Salamone JD

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Full name : Salamone John D

First name : John D

Mail : Department of Psychology, University of Connecticut, Storrs, CT 06269-1020

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Country : USA

Email : john.salamone@uconn.edu

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References (43)

Title : Induction of oral tremor in mice by the acetylcholinesterase inhibitor galantamine: Reversal with adenosine A antagonism - Podurgiel_2015_Pharmacol.Biochem.Behav_140_62
Author(s) : Podurgiel SJ , Spencer T , Kovner R , Baqi Y , Muller CE , Correa M , Salamone JD
Ref : Pharmacol Biochem Behav , 140 :62 , 2015
Abstract : Tremulous jaw movements (TJMs) have become a commonly used rat model of Parkinsonian tremor. TJMs can be induced by a number of neurochemical conditions that parallel those seen in human Parkinsonism, including DA depletion, DA antagonism, and cholinomimetic administration, and can be reduced by various antiparkinsonian agents. TJMs typically occur in bursts with the peak frequency in the range of 3-7.5Hz, which is similar to the Parkinsonian tremor frequency range. While the vast majority of this work has been done using rats, current efforts have focused on extending the TJM model to mice. The aim of the present studies was to establish a mouse model of Parkinsonian resting tremor using the anticholinesterase galantamine, and to investigate the effects of adenosine A2A antagonism on galantamine-induced TJMs. Galantamine significantly induced TJMs in a dose-dependent manner (0.5, 1.0, 1.5, 2.0, 2.5mg/kg IP). The TJMs tended to occur in bursts in the 3-7.5Hz frequency range, with a peak frequency of approximately 6Hz. Systemic administration of the adenosine A2A antagonist MSX-3 (2.5, 5.0, 10.0mg/kg) significantly attenuated galantamine-induced TJMs. Co-administration of MSX-3 also altered the local frequency of galantamine-induced TJMs, decreasing the peak frequency from approximately 6Hz to 5Hz, though the vast majority of TJMs remained in the frequency range characteristic of Parkinsonian resting tremor. These results indicate that adenosine A2A antagonism is capable of reducing anticholinesterase-induced TJMs in mice. Extending the TJM model to mice gives researchers an additional avenue for investigating drug-induced Parkinsonism and tremorogenesis, and could be a useful addition to the study of motor abnormalities observed in mouse genetic models of Parkinsonism.
ESTHER : Podurgiel_2015_Pharmacol.Biochem.Behav_140_62
PubMedSearch : Podurgiel_2015_Pharmacol.Biochem.Behav_140_62
PubMedID: 26459156

Title : Deep brain stimulation of the subthalamic nucleus reverses oral tremor in pharmacological models of parkinsonism: interaction with the effects of adenosine A2A antagonism - Collins-Praino_2013_Eur.J.Neurosci_38_2183
Author(s) : Collins-Praino LE , Paul NE , Ledgard F , Podurgiel SJ , Kovner R , Baqi Y , Muller CE , Senatus PB , Salamone JD
Ref : European Journal of Neuroscience , 38 :2183 , 2013
Abstract : Deep brain stimulation (DBS) of the subthalamic nucleus is increasingly being employed as a treatment for parkinsonian symptoms, including tremor. The present studies used tremulous jaw movements, a pharmacological model of tremor in rodents, to investigate the tremorolytic effects of subthalamic DBS in rats. Subthalamic DBS reduced the tremulous jaw movements induced by the dopamine D2 family antagonist pimozide and the D1 family antagonist ecopipam, as well as the cholinomimetics pilocarpine and galantamine. The ability of DBS to suppress tremulous jaw movements was dependent on the neuroanatomical locus being stimulated (subthalamic nucleus vs. a striatal control site), as well as the frequency and intensity of stimulation used. Importantly, administration of the adenosine A2A receptor antagonist MSX-3 reduced the frequency and intensity parameters needed to attenuate tremulous jaw movements. These results have implications for the clinical use of DBS, and future studies should determine whether adenosine A2A antagonism could be used to enhance the tremorolytic efficacy of subthalamic DBS at low frequencies and intensities in human patients.
ESTHER : Collins-Praino_2013_Eur.J.Neurosci_38_2183
PubMedSearch : Collins-Praino_2013_Eur.J.Neurosci_38_2183
PubMedID: 23600953

Title : Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors - Nunes_2013_Neurosci.Biobehav.Rev_37_2015
Author(s) : Nunes EJ , Randall PA , Podurgiel S , Correa M , Salamone JD
Ref : Neurosci Biobehav Rev , 37 :2015 , 2013
Abstract : Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Although nucleus accumbens (NAc) DA depletions or antagonism leave aspects of appetite and primary food motivation intact, rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A2A antagonists can reverse the effects of DA D2 antagonists on effort-related choice, and that stimulation of adenosine A2A receptors produces behavioral effects that are similar to those induced by DA antagonism. The present review summarizes the literature on the role of NAc DA and adenosine in effort-related processes, and also presents original data on the effects of local stimulation of muscarinic acetylcholine receptors in NAc core. Local injections of the muscarinic agonist pilocarpine directly into NAc core produces shifts in effort-related choice behavior similar to those induced by DA antagonism or A2A receptor stimulation, decreasing lever pressing but increasing chow intake in rats responding on a concurrent fixed ratio/chow feeding choice task. In contrast, injections into a neostriatal control site dorsal to the NAc were ineffective. The actions of pilocarpine on this task were attenuated by co-administration of the muscarinic antagonist scopolamine. Thus, drugs that act on DA, adenosine A2A, and muscarinic receptors regulate effort-related choice behavior, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, fatigue or anergia that can be observed in depression and other disorders.
ESTHER : Nunes_2013_Neurosci.Biobehav.Rev_37_2015
PubMedSearch : Nunes_2013_Neurosci.Biobehav.Rev_37_2015
PubMedID: 23583616

Title : Tremorolytic effects of safinamide in animal models of drug-induced parkinsonian tremor - Podurgiel_2013_Pharmacol.Biochem.Behav_105_105
Author(s) : Podurgiel S , Collins-Praino LE , Yohn S , Randall PA , Roach A , Lobianco C , Salamone JD
Ref : Pharmacol Biochem Behav , 105 :105 , 2013
Abstract : Safinamide is an alpha-aminoamide derivative that is currently in Phase III clinical trial development as an add-on therapy to levodopa or dopamine agonists for patients with Parkinson's disease. Safinamide is a monoamine oxidase B inhibitor with additional non-dopaminergic actions. The present experiments were performed to evaluate the ability of safinamide to attenuate parkinsonian motor impairments using the tremulous jaw movement model, an animal model of parkinsonian tremor. In rats, tremulous jaw movements can be induced with dopamine (DA) antagonists, DA depletion, and cholinomimetics, and can be reversed by various antiparkinsonian drugs, including L-DOPA, DA agonists, anticholinergics and adenosine A2A antagonists. In these present experiments, tremulous jaw movements were induced with the anticholinesterase galantamine (3.0mg/kg IP), the muscarinic agonist pilocarpine (0.5mg/kg IP), and the dopamine D2 antagonist pimozide (1.0mg/kg IP). Safinamide significantly reduced the number of tremulous jaw movements induced by galantamine, pilocarpine, and pimozide, with consistent effects across all three drugs at a dose range of 5.0-10.0mg/kg. The results of this study support the use of safinamide as a treatment for parkinsonian tremor.
ESTHER : Podurgiel_2013_Pharmacol.Biochem.Behav_105_105
PubMedSearch : Podurgiel_2013_Pharmacol.Biochem.Behav_105_105
PubMedID: 23360954

Title : Conditional neural knockout of the adenosine A(2)A receptor and pharmacological A(2)A antagonism reduce pilocarpine-induced tremulous jaw movements: Studies with a mouse model of parkinsonian tremor - Salamone_2013_Eur.Neuropsychopharmacol_23_972
Author(s) : Salamone JD , Collins-Praino LE , Pardo M , Podurgiel SJ , Baqi Y , Muller CE , Schwarzschild MA , Correa M
Ref : European Neuropsychopharmacology , 23 :972 , 2013
Abstract : Tremulous jaw movements are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rats, tremulous jaw movements can be induced by a number of conditions that parallel those seen in human parkinsonism, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Moreover, tremulous jaw movements in rats can be attenuated using antiparkinsonian agents such as L-DOPA, dopamine agonists, muscarinic antagonists, and adenosine A(2)A antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A(2)A antagonism, and a conditional neuronal knockout of adenosine A(2)A receptors, on cholinomimetic-induced tremulous jaw movements. The muscarinic agonist pilocarpine significantly induced tremulous jaw movements in a dose-dependent manner (0.25-1.0mg/kg IP). These movements occurred largely in the 3-7.5 Hz local frequency range. Administration of the adenosine A(2)A antagonist MSX-3 (2.5-10.0 mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A(2)A receptor knockout mice showed a significant reduction in pilocarpine-induced tremulous jaw movements compared to littermate controls. These results demonstrate the feasibility of using the tremulous jaw movement model in mice, and indicate that adenosine A(2)A receptor antagonism and deletion are capable of reducing cholinomimetic-induced tremulous jaw movements in mice. Future studies should investigate the effects of additional genetic manipulations using the mouse tremulous jaw movement model.
ESTHER : Salamone_2013_Eur.Neuropsychopharmacol_23_972
PubMedSearch : Salamone_2013_Eur.Neuropsychopharmacol_23_972
PubMedID: 22947264

Title : Extracellular GABA in globus pallidus increases during the induction of oral tremor by haloperidol but not by muscarinic receptor stimulation - Collins-Praino_2012_Behav.Brain.Res_234_129
Author(s) : Collins-Praino LE , Podurgiel SJ , Kovner R , Randall PA , Salamone JD
Ref : Behavioural Brain Research , 234 :129 , 2012
Abstract : Tremulous jaw movements in rats can be induced by several conditions associated with parkinsonism and tremorogenesis, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Previous research indicates that neostriatal mechanisms are involved in the generation of tremulous jaw movements, but the striatal output pathways involved in these movements remain uncertain. One important pathway for striatal output is the GABAergic striatopallidal system. The present studies were undertaken to determine if extracellular levels of GABA in globus pallidus are associated with the induction of tremulous jaw movements by either a dopamine D2 antagonist (haloperidol) or a cholinomimetic (the muscarinic agonist pilocarpine). The first experiment studied the effects of both acute and repeated (i.e. 8 days) administration of the D2 antagonist haloperidol. In the second experiment, the effect of acute administration of the muscarinic agonist pilocarpine on GABA levels in the globus pallidus was examined. In both experiments, behavioral observations of tremulous jaw movements were conducted in parallel with the collection of microdialysis samples. Acute and repeated haloperidol treatment induced tremulous jaw movements, and significantly elevated extracellular GABA in globus pallidus. Pooling across all treatment groups, there was a significant positive correlation between pallidal GABA levels and the number of tremulous jaw movements induced during the first three samples collected after injection. However, injection of 4.0mg/kg pilocarpine had no effect on pallidal GABA release, despite the robust induction of tremulous jaw movements. These results indicate that the tremulous jaw movements induced by dopamine D2 antagonism and those induced through muscarinic receptor stimulation may be generated via distinct mechanisms.
ESTHER : Collins-Praino_2012_Behav.Brain.Res_234_129
PubMedSearch : Collins-Praino_2012_Behav.Brain.Res_234_129
PubMedID: 22728308

Title : Oral tremor induced by galantamine in rats: a model of the parkinsonian side effects of cholinomimetics used to treat Alzheimer's disease - Collins_2011_Pharmacol.Biochem.Behav_99_414
Author(s) : Collins LE , Paul NE , Abbas SF , Leser CE , Podurgiel SJ , Galtieri DJ , Chrobak JJ , Baqi Y , Muller CE , Salamone JD
Ref : Pharmacol Biochem Behav , 99 :414 , 2011
Abstract : Anticholinesterases are the most common treatment for Alzheimer's disease, and, in recent years, a new group of cholinesterase inhibitors (i.e. rivastigmine, galantamine, and donepezil) has become available. Although these drugs improve cognitive symptoms, they also can induce or exacerbate parkinsonian symptoms, including tremor. The present studies were conducted to determine if galantamine induces tremulous jaw movements, a rodent model of parkinsonian tremor, and to investigate whether these oral motor impairments can be reversed by co-administration of adenosine A(2A) antagonists. The first experiment demonstrated that systemic injections of galantamine (0.75-6.0 mg/kg I.P.) induced a dose-related increase in tremulous jaw movements in rats. In a second study, co-administration of the muscarinic antagonist scopolamine (0.0156-0.25 mg/kg I.P.) produced a dose dependent suppression of tremulous jaw movements induced by a 3.0 mg/kg dose of galantamine, indicating that galantamine induces these tremulous oral movements through actions on muscarinic acetylcholine receptors. In two additional studies, analyses of freeze-frame video and electromyographic activity recorded from the lateral temporalis muscle indicated that the local frequency of these galantamine-induced jaw movements occurs in the 3-7 Hz frequency range that is characteristic of parkinsonian tremor. In the final experiment, the adenosine A(2A) antagonist MSX-3 significantly attenuated the tremulous jaw movements induced by the 3.0mg/kg dose of galantamine, which is consistent with the hypothesis that co-administration of adenosine A(2A) antagonists may be beneficial in reducing parkinsonian motor impairments induced by anticholinesterase treatment.
ESTHER : Collins_2011_Pharmacol.Biochem.Behav_99_414
PubMedSearch : Collins_2011_Pharmacol.Biochem.Behav_99_414
PubMedID: 21640750

Title : Pharmacological and physiological characterization of the tremulous jaw movement model of parkinsonian tremor: potential insights into the pathophysiology of tremor - Collins-Praino_2011_Front.Syst.Neurosci_5_49
Author(s) : Collins-Praino LE , Paul NE , Rychalsky KL , Hinman JR , Chrobak JJ , Senatus PB , Salamone JD
Ref : Front Syst Neurosci , 5 :49 , 2011
Abstract : Tremor is a cardinal symptom of parkinsonism, occurring early on in the disease course and affecting more than 70% of patients. Parkinsonian resting tremor occurs in a frequency range of 3-7 Hz and can be resistant to available pharmacotherapy. Despite its prevalence, and the significant decrease in quality of life associated with it, the pathophysiology of parkinsonian tremor is poorly understood. The tremulous jaw movement (TJM) model is an extensively validated rodent model of tremor. TJMs are induced by conditions that also lead to parkinsonism in humans (i.e., striatal DA depletion, DA antagonism, and cholinomimetic activity) and reversed by several antiparkinsonian drugs (i.e., DA precursors, DA agonists, anticholinergics, and adenosine A(2A) antagonists). TJMs occur in the same 3-7 Hz frequency range seen in parkinsonian resting tremor, a range distinct from that of dyskinesia (1-2 Hz), and postural tremor (8-14 Hz). Overall, these drug-induced TJMs share many characteristics with human parkinsonian tremor, but do not closely resemble tardive dyskinesia. The current review discusses recent advances in the validation of the TJM model, and illustrates how this model is being used to develop novel therapeutic strategies, both surgical and pharmacological, for the treatment of parkinsonian resting tremor.
ESTHER : Collins-Praino_2011_Front.Syst.Neurosci_5_49
PubMedSearch : Collins-Praino_2011_Front.Syst.Neurosci_5_49
PubMedID: 21772815

Title : Oral tremor induced by the muscarinic agonist pilocarpine is suppressed by the adenosine A2A antagonists MSX-3 and SCH58261, but not the adenosine A1 antagonist DPCPX - Collins_2010_Pharmacol.Biochem.Behav_94_561
Author(s) : Collins LE , Galtieri DJ , Brennum LT , Sager TN , Hockemeyer J , Muller CE , Hinman JR , Chrobak JJ , Salamone JD
Ref : Pharmacol Biochem Behav , 94 :561 , 2010
Abstract : Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A(2A) antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A(2A) antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0mg/kg dose of pilocarpine, both MSX-3 and the adenosine A(2A) antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5mg/kg pilocarpine. Systemic administration of the adenosine A(1) antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A(2A) receptors, but DPCPX did not. The results of these studies support the use of adenosine A(2A) antagonists for the treatment of tremor.
ESTHER : Collins_2010_Pharmacol.Biochem.Behav_94_561
PubMedSearch : Collins_2010_Pharmacol.Biochem.Behav_94_561
PubMedID: 19958787

Title : Effects of the adenosine A 2A antagonist KW 6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide - Betz_2009_Neurosci_163_97
Author(s) : Betz AJ , Vontell R , Valenta J , Worden L , Sink KS , Font L , Correa M , Sager TN , Salamone JD
Ref : Neuroscience , 163 :97 , 2009
Abstract : Typical antipsychotic drugs, including haloperidol and pimozide, have been shown to produce parkinsonian motor effects such as akinesia and tremor. Furthermore, there is an antagonistic interaction between adenosine A(2A) and dopamine D(2) receptors in the basal ganglia, which is important for motor functions related to the production of parkinsonian symptoms. Several experiments were conducted to assess the effects of the selective adenosine A(2A) antagonist KW 6002 on both the motor and cellular effects of subchronic administration of pimozide. The motor test employed was tremulous jaw movements, which is used as a model of parkinsonian tremor. In addition, c-Fos expression in the ventrolateral neostriatum, which is the striatal area most associated with tremulous jaw movements, was used as a marker of striatal cell activity in animals that were tested in the behavioral experiments. Repeated administration of 1.0 mg/kg pimozide induced tremulous jaw movements and increased ventrolateral striatal c-Fos expression, while administration of 20.0 mg/kg of the atypical antipsychotic quetiapine did not. The tremulous jaw movements induced by pimozide were significantly reduced by co-administration of either the adenosine A(2A) antagonist KW 6002 or the muscarinic antagonist tropicamide. Pimozide-induced increases in ventrolateral striatal c-Fos expression were reduced by a behaviorally effective dose of KW 6002, but c-Fos expression in pimozide-treated rats was actually increased by tropicamide. These results indicate that two different drug manipulations that act to reduce tremulous jaw movements can have different effects on DA antagonist-induced c-Fos expression, suggesting that adenosine A(2A) antagonism and muscarinic receptor antagonism exert their motor effects by acting on different striatal circuits.
ESTHER : Betz_2009_Neurosci_163_97
PubMedSearch : Betz_2009_Neurosci_163_97
PubMedID: 19467297

Title : The novel cannabinoid CB1 receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats - Sink_2008_Neuropsychopharmacology_33_946
Author(s) : Sink KS , McLaughlin PJ , Wood JA , Brown C , Fan P , Vemuri VK , Peng Y , Olszewska T , Thakur GA , Makriyannis A , Parker LA , Salamone JD
Ref : Neuropsychopharmacology , 33 :946 , 2008
Abstract : Drugs that interfere with cannabinoid CB1 transmission suppress various food-motivated behaviors, and it has been suggested that such drugs could be useful as appetite suppressants. Biochemical studies indicate that most of these drugs assessed thus far have been CB1 inverse agonists, and although they have been shown to suppress food intake, they also appear to induce nausea and malaise. The present studies were undertaken to characterize the behavioral effects of AM4113, which is a CB1 neutral antagonist, and to examine whether this drug can reduce food-reinforced behaviors and feeding on diets with varying macronutrient compositions. Biochemical data demonstrated that AM4113 binds to CB1 receptors, but does not show inverse agonist properties (ie no effects on cyclic-AMP production). In tests of spontaneous locomotion and analgesia, AM4113 reversed the effects of the CB1 agonist AM411. AM4113 suppressed food-reinforced operant responding with rats responding on fixed ratio (FR) 1 and 5 schedules of reinforcement in a dose-dependent manner, and also suppressed feeding on high-fat, high-carbohydrate, and lab chow diets. However, in the same dose range that suppressed feeding, AM4113 did not induce conditioned gaping, which is a sign of nausea and food-related malaise in rats. These results suggest that AM4113 may decrease appetite by blocking endogenous cannabinoid tone, and that this drug may be less associated with nausea than CB1 inverse agonists.
ESTHER : Sink_2008_Neuropsychopharmacology_33_946
PubMedSearch : Sink_2008_Neuropsychopharmacology_33_946
PubMedID: 17581535

Title : The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors - Betz_2007_Psychopharmacology.(Berl)_194_347
Author(s) : Betz AJ , McLaughlin PJ , Burgos M , Weber SM , Salamone JD
Ref : Psychopharmacology (Berl) , 194 :347 , 2007
Abstract : RATIONALE: Nonselective muscarinic acetylcholine antagonists have been used for several years as antiparkinsonian drugs. However, there are at least five subtypes of muscarinic receptor (M1-5). Neostriatal M4 receptors have been implicated in aspects of motor function, and it has been suggested that M4 antagonists could be used as treatments for parkinsonism. OBJECTIVE: Currently, there is a lack of highly selective M4 antagonists that readily penetrate the blood brain barrier. Thus, the present studies focused upon the effects of tropicamide, a muscarinic acetylcholine receptor antagonist with moderate binding selectivity for the M4 receptor subtype. MATERIALS AND
METHODS: Tremulous jaw movements were used as a model of parkinsonian tremor in these studies, and the effects of tropicamide were compared with those of the nonselective muscarinic antagonist atropine.
RESULTS: Tropicamide suppressed the tremulous jaw movements induced by the muscarinic agonist pilocarpine and the dopamine antagonist pimozide. Analysis of the dose-response curves indicated that tropicamide showed approximately the same potency as atropine for suppression of pilocarpine-induced jaw movements but was more potent than atropine on the suppression of pimozide-induced jaw movements. In contrast, atropine was more potent than tropicamide in terms of impairing performance on visual stimulus detection and delayed nonmatch-to-position tasks.
CONCLUSIONS: These studies demonstrate that tropicamide, which currently is used clinically for ophthalmic purposes, can exert actions that are consistent with antiparkinsonian effects. Moreover, the different pattern of effects shown by tropicamide compared to those of atropine on motor vs cognitive tasks could be due to the modest M4 selectivity shown by tropicamide.
ESTHER : Betz_2007_Psychopharmacology.(Berl)_194_347
PubMedSearch : Betz_2007_Psychopharmacology.(Berl)_194_347
PubMedID: 17594079

Title : The novel cannabinoid agonist AM 411 produces a biphasic effect on accuracy in a visual target detection task in rats - McLaughlin_2005_Behav.Pharmacol_16_477
Author(s) : McLaughlin PJ , Brown CM , Winston KM , Thakur G , Lu D , Makriyannis A , Salamone JD
Ref : Behav Pharmacol , 16 :477 , 2005
Abstract : Cannabinoid agonists have been shown to produce dose-related impairments in several measures of cognitive performance. However, it is unclear if low doses of cannabinoid CB1 agonists, or CB1 antagonists, can facilitate aspects of stimulus detection. The present study employed an operant procedure involving visual stimulus detection in rats. The task was found to be sensitive to the muscarinic acetylcholine antagonist scopolamine. The CB1 antagonist AM 251 did not affect stimulus detection processes across a broad range of doses. However, the novel CB1 agonist AM 411 produced a biphasic effect, with the two lowest doses (0.25 and 0.5 mg/kg) enhancing accuracy. AM 411 changed patterns of responding toward runs of consecutive errors on only one of the two levers. It produced a biphasic effect on consecutive errors on the lever associated with a higher level of errors, with decreases in errors following the lower doses (0.25 and 0.5 mg/kg) and increases following the highest dose (2.0 mg/kg). These effects were not accompanied by changes in measures of bias commonly used to uncover such patterns in rodent operant models of cognitive performance. In contrast to the cognitive impairment seen after administration of moderate to high doses of CB1 agonists, it appears that low doses of some CB1 agonists may be capable of enhancing stimulus detection processes.
ESTHER : McLaughlin_2005_Behav.Pharmacol_16_477
PubMedSearch : McLaughlin_2005_Behav.Pharmacol_16_477
PubMedID: 16148454

Title : Dopamine agonists suppress cholinomimetic-induced tremulous jaw movements in an animal model of Parkinsonism: tremorolytic effects of pergolide, ropinirole and CY 208-243 - Salamone_2005_Behav.Brain.Res_156_173
Author(s) : Salamone JD , Carlson BB , Rios C , Lentini E , Correa M , Wisniecki A , Betz A
Ref : Behavioural Brain Research , 156 :173 , 2005
Abstract : Considerable evidence indicates that cholinomimetic-induced tremulous jaw movements in rats share many characteristics with human Parkinsonian tremor, and several antiparkinsonian drugs suppress cholinomimetic-induced tremulous jaw movements. The present study investigated three different types of dopamine agonists, which have known antiparkinsonian characteristics, for their ability to suppress the tremulous jaw movements induced by tacrine (5.0 mg/kg). The non-selective dopamine agonist pergolide, a widely used antiparkinsonian drug, was highly potent at suppressing tacrine-induced jaw movements (e.g. 0.125-1.0 mg/kg). The selective D2 agonist ropinirole, which also is used clinically as an antiparkinsonian drug, suppressed jaw movements in the dose range of 2.5-20.0 mg/kg. The D1 agonist CY 208-243, which has been reported to suppress tremor, also reduced jaw movement activity (4.0 mg/kg). Across several studies, the rank order of potency for suppressing cholinomimetic-induced jaw movements in rats is related to the potency for producing antiparkinsonian effects in humans. Together with previous studies, the present results suggest that cholinomimetic-induced jaw movements in rats can be used to characterize dopaminergic antiparkinsonian agents and to investigate the basal ganglia circuits involved in the generation of tremulous movements.
ESTHER : Salamone_2005_Behav.Brain.Res_156_173
PubMedSearch : Salamone_2005_Behav.Brain.Res_156_173
PubMedID: 15582103

Title : Quetiapine (Seroquel) shows a pattern of behavioral effects similar to the atypical antipsychotics clozapine and olanzapine: studies with tremulous jaw movements in rats - Betz_2005_Psychopharmacology.(Berl)_179_383
Author(s) : Betz A , Ishiwari K , Wisniecki A , Huyn N , Salamone JD
Ref : Psychopharmacology (Berl) , 179 :383 , 2005
Abstract : RATIONALE: Previous studies demonstrated that clozapine and olanzapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing. OBJECTIVE: The present studies were undertaken to evaluate the novel atypical antipsychotic quetiapine using the jaw movement model.
METHODS: The effect of acute quetiapine on the suppression of tacrine-induced tremulous jaw movements was examined. To determine the relative potency of this effect compared with other behavioral effects of quetiapine, suppression of lever pressing also was studied. In other studies, rats received quetiapine for 14 consecutive days to study the effects of repeated injections of this drug.
RESULTS: Acute quetiapine injections decreased tacrine-induced jaw movements and lever pressing. The ratio of the ED50 for suppression of jaw movements divided by the ED50 for suppression of lever pressing was used as an index of liability to produce motor side effects, and the present results demonstrate that quetiapine has a ratio similar to that previously shown for clozapine and olanzapine. In the repeated-administration studies, quetiapine failed to induce jaw movements. On day 14, quetiapine reduced tacrine-induced tremulous jaw movements, and in a parallel experiment quetiapine significantly suppressed lever pressing on days 1-14. Repeated injections of quetiapine reduced tacrine-induced jaw movements over a dose range lower than that required for suppression of lever pressing.
CONCLUSIONS: On tests of jaw movement activity and lever pressing after both acute and repeated drug administration, quetiapine showed a profile somewhat similar to clozapine and olanzapine. A theoretical model is offered suggesting that atypical antipsychotics that act on 5-HT or muscarinic receptors have intrinsic antiparkinsonian actions that work in opposition to the motor effects produced by dopamine antagonism.
ESTHER : Betz_2005_Psychopharmacology.(Berl)_179_383
PubMedSearch : Betz_2005_Psychopharmacology.(Berl)_179_383
PubMedID: 15619122

Title : The GABA uptake inhibitor beta-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis - Ishiwari_2004_J.Neurosci.Methods_140_39
Author(s) : Ishiwari K , Mingote S , Correa M , Trevitt JT , Carlson BB , Salamone JD
Ref : Journal of Neuroscience Methods , 140 :39 , 2004
Abstract : Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.
ESTHER : Ishiwari_2004_J.Neurosci.Methods_140_39
PubMedSearch : Ishiwari_2004_J.Neurosci.Methods_140_39
PubMedID: 15589332

Title : Local injections of the 5-hydroxytryptamine antagonist mianserin into substantia nigra pars reticulata block tremulous jaw movements in rats: studies with a putative model of Parkinsonian tremor - Carlson_2003_Psychopharmacology.(Berl)_165_229
Author(s) : Carlson BB , Wisniecki A , Salamone JD
Ref : Psychopharmacology (Berl) , 165 :229 , 2003
Abstract : RATIONALE: Atypical antipsychotics such as clozapine and olanzapine have a low liability for producing motor side effects. In addition to being D2 antagonists, these drugs have a complex binding profile that includes affinity for muscarinic, alpha, H1, and various serotonin receptors. Previous work in rats has shown that atypical antipsychotics suppress tremulous jaw movements induced by the anticholinesterase tacrine in rats. Cholinomimetic-induced jaw movements are a putative model of parkinsonian tremor, and the ability of antipsychotic drugs to suppress these movements in rats is correlated with motor side-effect liability in humans. OBJECTIVE: The present work was undertaken to study the role of central serotonin receptors in the generation of cholinomimetic-induced jaw movements.
RESULTS: Systemic injections of the serotonin antagonist mianserin suppressed tacrine-induced jaw movements, with an ED(50) of 2.77 mg/kg. Local injections of mianserin directly into substantia nigra pars reticulata (SNr) also suppressed tacrine-induced jaw movements. Injections into ventrolateral neostriatum, or a control site dorsal to SNr, failed to have any effects on jaw movement activity.
CONCLUSIONS: These studies suggest that atypical antipsychotics may act both on striatal muscarinic receptors and nigral serotonin receptors to suppress jaw movement activity. It is possible that the unique motor properties of atypical antipsychotics result from actions on multiple receptors in several brain areas. The precise serotonin receptor subtype involved in these effects is unknown, and future work will examine the effects of drugs that act selectively on 5-HT(2A) and 5-HT(2C) receptors.
ESTHER : Carlson_2003_Psychopharmacology.(Berl)_165_229
PubMedSearch : Carlson_2003_Psychopharmacology.(Berl)_165_229
PubMedID: 12420151

Title : Motor effects of GABA(A) antagonism in globus pallidus: studies of locomotion and tremulous jaw movements in rats - Wisniecki_2003_Psychopharmacology.(Berl)_170_140
Author(s) : Wisniecki A , Correa M , Arizzi MN , Ishiwari K , Salamone JD
Ref : Psychopharmacology (Berl) , 170 :140 , 2003
Abstract : RATIONALE: Although most rodent studies related to parkinsonian symptoms have focused on locomotion, tremulous jaw movements also have been used as a rodent model of tremor for investigating the circuitry of the basal ganglia. OBJECTIVE: There are multiple pathways involved in the generation of parkinsonian symptoms. The globus pallidus is a basal ganglia relay nucleus, and the present study was conducted to investigate the effect of pallidal GABA antagonism on locomotion and tremulous jaw movements.
METHODS: Suppression of locomotion and induction of tremulous jaw movements were produced by repeated (i.e., 14 day) systemic administration of the dopamine D2 antagonist haloperidol, and by acute systemic injection of the muscarinic agonist pilocarpine. The GABA(A) antagonist bicuculline was injected into the globus pallidus, and its effects on locomotion in haloperidol- and pilocarpine-treated rats were assessed in the first group of experiments. In the second group of experiments, the effects of intrapallidal infusions of bicuculline on haloperidol- and pilocarpine-induced jaw movements were observed.
RESULTS: Pallidal GABA antagonism stimulated locomotion when no other treatment was present, and also when animals were coadministered haloperidol or pilocarpine. Bicuculline suppressed haloperidol-induced jaw movements in a dose-related manner, and had no effect on pilocarpine-induced jaw movements.
CONCLUSIONS: These results support the notion that there are distinct pathways conveying basal ganglia outflow and demonstrate that the striatopallidal pathway is involved in the generation of the haloperidol-induced tremulous jaw movements. These findings are consistent with some features of current models of basal ganglia function and may lead to an understanding of the specific mechanisms that generate parkinsonian symptoms.
ESTHER : Wisniecki_2003_Psychopharmacology.(Berl)_170_140
PubMedSearch : Wisniecki_2003_Psychopharmacology.(Berl)_170_140
PubMedID: 12827348

Title : Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents implications for cholinergic involvement in parkinsonism - Salamone_2001_Life.Sci_68(22-23)_2579
Author(s) : Salamone JD , Correa M , Carlson BB , Wisniecki A , Mayorga AJ , Nisenbaum E , Nisenbaum L , Felder CC
Ref : Life Sciences , 68 :2579 , 2001
Abstract : Several studies have shown that a number of pharmacological and neurochemical conditions in rats can induce jaw movements that are described as "vacuous" or "tremulous". For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevertheless, considerable evidence now indicates that the non-directed, chewing-like movements induced by cholinomimetics have many of the characteristics of parkinsonian tremor. These movements are characterized largely by vertical deflections of the jaw, which occur in the same 3-7 Hz peak frequency that is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropinirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M4 receptors in the ventrolateral neostriatum in the generation of tremulous jaw movements. Mice also show cholinomimetic-induced jaw movements, and M4 receptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are consistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor.
ESTHER : Salamone_2001_Life.Sci_68(22-23)_2579
PubMedSearch : Salamone_2001_Life.Sci_68(22-23)_2579
PubMedID: 11392629

Title : Effects of H1 antagonists on cholinomimetic-induced tremulous jaw movements: studies of diphenhydramine, doxepin, and mepyramine - Carlson_2000_Pharmacol.Biochem.Behav_65_683
Author(s) : Carlson BB , Trevitt JT , Salamone JD
Ref : Pharmacol Biochem Behav , 65 :683 , 2000
Abstract : In several previous studies, tremulous jaw movements in rats have been used to assess the effects of antiparkinsonian drugs and atypical antipsychotics. Because antihistamines such as diphenhydramine are used as antiparkinsonian agents, and atypical antipsychotic drugs such as clozapine and olanzapine have high affinity for histamine H1 receptors, the present study investigated the effects of H1 antagonists on cholinomimetic-induced jaw movements. Diphenhydramine, doxepin, and mepyramine (all injected IP 2.5-20.0 mg/kg) were assessed for their ability to block the jaw movements induced by 5.0 mg/kg of the anticholinesterase tacrine. Within this dose range, only diphenhydramine produced a robust and significant reduction in jaw movement activity. Thus, diphenhydramine was subjected to further testing, which employed procedures previously used to assess the effects of other antitremorogenic drugs, such as clozapine. Diphenhydramine did not induce jaw movement activity. In addition to suppressing jaw movement activity after acute injections, diphenhydramine also suppressed tacrine-induced jaw movements after repeated (14-day) administration. In summary, the present results show that diphenhydramine suppresses cholinomimetic-induced jaw movements, an effect that is similar to other antiparkinsonian or antitremor drugs such as anticholinergics, L-DOPA, DA antagonists, and clozapine. Nevertheless, doxepin produced only mild effects, and mepyramine, which has a higher affinity and selectivity than diphenhydramine for H1 receptors, failed to suppress cholinomimetic-induced jaw movements. These results suggest that diphenhydramine suppresses tremulous movements through a mechanism that does not depend upon antagonism of histamine H1 receptors.
ESTHER : Carlson_2000_Pharmacol.Biochem.Behav_65_683
PubMedSearch : Carlson_2000_Pharmacol.Biochem.Behav_65_683
PubMedID: 10764923

Title : Behavioral assessment of atypical antipsychotics in rats: studies of the effects of olanzapine (Zyprexa) - Trevitt_1999_Psychopharmacology.(Berl)_145_309
Author(s) : Trevitt JT , Carlson BB , Salamone JD
Ref : Psychopharmacology (Berl) , 145 :309 , 1999
Abstract : RATIONALE: Previous work has shown that clozapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing. OBJECTIVE: The novel atypical antipsychotic olanzapine was assessed in these behavioral tests.
METHODS: The effect of acute olanzapine on the suppression of tacrine-induced tremulous jaw movements was examined. In order to determine the relative potency of this effect compared with other behavioral effects of olanzapine, suppression of lever pressing also was studied. In a second series of experiments, rats received olanzapine for 14 consecutive days to study the effects of repeated injections of this drug on jaw movements and lever pressing.
RESULTS: Acute olanzapine administration decreased tacrine-induced jaw movements (ED50: 0.4 mg/kg), and also reduced lever pressing (ED50: 1.12 mg/kg). The ratio of the ED50 for suppression of jaw movements to that for suppression of lever pressing was used as an index of liability to produce extrapyramidal side effects, and the present results demonstrate that olanzapine has a ratio similar to that previously shown for clozapine. In the repeated administration studies, rats were observed on day 13 of drug treatment for the ability of olanzapine to induce jaw movements, and olanzapine failed to induce jaw movements. On day 14, olanzapine reduced tacrine-induced tremulous jaw movements (ED50: 1.12 mg/kg). In a separate experiment, olanzapine significantly suppressed lever pressing, and this effect showed sensitization with repeated administration (day 14, ED50: 0.76 mg/kg). Thus, repeated injections of olanzapine reduced tacrine-induced jaw movements in a dose range similar to or slightly higher than that which suppressed lever pressing.
CONCLUSIONS: On tests of jaw-movement activity and lever pressing after both acute and repeated drug administration, olanzapine demonstrated a profile somewhat similar to clozapine, and both of these drugs differ substantially from the typical antipsychotic haloperidol.
ESTHER : Trevitt_1999_Psychopharmacology.(Berl)_145_309
PubMedSearch : Trevitt_1999_Psychopharmacology.(Berl)_145_309
PubMedID: 10494580

Title : Characterization of the muscarinic receptor subtype mediating pilocarpine-induced tremulous jaw movements in rats - Mayorga_1999_Eur.J.Pharmacol_364_7
Author(s) : Mayorga AJ , Cousins MS , Trevitt JT , Conlan A , Gianutsos G , Salamone JD
Ref : European Journal of Pharmacology , 364 :7 , 1999
Abstract : Four muscarinic receptor antagonists with varying selectivities for the four pharmacologically-defined muscarinic receptor subtypes (M1-M4) were administered into the lateral ventricle to determine their relative potency in reducing tremulous jaw movements induced by i.p. injection of the muscarinic receptor agonist pilocarpine (4.0 mg/kg). All four muscarinic receptor antagonists reduced tremulous jaw movements in a dose-dependent manner, with the following rank order of potency: scopolamine > methoctramine > or = telenzepine > pirenzepine. This pattern is inconsistent with the rank order of affinity of these agents at the muscarinic M1 receptor, and is consistent with their rank order of affinity at muscarinic M2 or M4 receptors. Because tremulous jaw movements are related to striatal function, and the muscarinic M4 receptor is more predominant than the muscarinic M2 receptor as a post-synaptic receptor in striatum, the present results suggest that pilocarpine induces jaw movements due to muscarinic M4 receptor stimulation. In view of the hypothesized relation between parkinsonism and cholinomimetic-induced jaw movements, these data suggest that a centrally-acting muscarinic M4 receptor antagonist could be useful as an antiparkinsonian agent.
ESTHER : Mayorga_1999_Eur.J.Pharmacol_364_7
PubMedSearch : Mayorga_1999_Eur.J.Pharmacol_364_7
PubMedID: 9920179

Title : Effects of striatal injections of 8-bromo-cyclic-AMP on pilocarpine-induced tremulous jaw movements in rats - Mayorga_1999_Brain.Res_829_180
Author(s) : Mayorga AJ , Gianutsos G , Salamone JD
Ref : Brain Research , 829 :180 , 1999
Abstract : Previous work has suggested that muscarinic agonist-induced jaw movements in rats were related to stimulation of M4 receptors, and that these movements could be suppressed by a full D1 agonist. In view of the involvement of cyclic-adenosine monophosphate (c-AMP) mechanisms in the response to stimulation of these two receptors, the present study investigated the effects of 8-bromo-c-AMP, which is a cell permeable analogue of c-AMP. In the first experiment, it was shown that local infusion of 8-bromo-c-AMP directly into ventrolateral striatum (VLS) was able to suppress the jaw movements induced by pilocarpine. The suppressive effects of 8-bromo-c-AMP occurred within a dose range of 5.0-10.0 microg. Injections of the highest dose of 8-bromo-c-AMP (10.0 microg) directly into the neocortex overlying the VLS had no significant effects on pilocarpine-induced jaw movements. These data demonstrate that mimicking the effects of c-AMP by administration of 8-bromo-c-AMP can suppress cholinomimetic-induced jaw movements. In addition, the present results suggest that one manifestation of the acetylcholine/dopamine interaction in striatum is that M4 and D1 receptors may interact to regulate c-AMP production.
ESTHER : Mayorga_1999_Brain.Res_829_180
PubMedSearch : Mayorga_1999_Brain.Res_829_180
PubMedID: 10350545

Title : Striatal and nigral D1 mechanisms involved in the antiparkinsonian effects of SKF 82958 (APB): studies of tremulous jaw movements in rats - Mayorga_1999_Psychopharmacology.(Berl)_143_72
Author(s) : Mayorga AJ , Trevitt JT , Conlan A , Gianutsos G , Salamone JD
Ref : Psychopharmacology (Berl) , 143 :72 , 1999
Abstract : RATIONALE: Previous work has demonstrated that cholinomimetic-induced tremulous jaw movements in rats have temporal and pharmacological characteristics similar to parkinsonian tremor. OBJECTIVE: This rodent model was used to characterize the putative antiparkinsonian effects of the full D1 dopamine receptor agonist, SKF 82958.
METHODS: Jaw movement activity was induced by the muscarine agonist pilocarpine (4.0 mg/kg IP), and a series of experiments studied the pharmacological characteristics of the reversal of pilocarpine-induced jaw movements by SKF 82958.
RESULTS: SKF 82958 (0.5-2.0 mg/kg IP) reduced the tremulous jaw movements induced by pilocarpine. The suppressive effects of SKF 82958 on jaw movements were dose-dependently reversed by systemic pretreatment with the selective D1 dopamine receptor antagonist SCH 23390 (0.025-0.2 mg/kg IP); SCH 23390 was about 16 times more potent than the D2 antagonist raclopride at reversing the effects of SKF 82958. Intracranial injection of SCH 23390 (0.5-2.0 micrograms/side) into the ventrolateral striatum, the rodent homologue of the human ventral putamen, dose-dependently reversed the reduction of pilocarpine-induced jaw movements produced by SKF 82958. Intracranial injection of SCH 23390 (0.5-2.0 micrograms/side) into the substantia nigra pars reticulata also dose-dependently reversed the reduction by SKF 82958 of pilocarpine-induced jaw movements. Injections of SCH 23390 (2.0 micrograms/side) into control sites dorsal to the striatum or substantia nigra had no effects on the action of SKF 82958. Intranigral (SNr) injections of the GABA-A antagonist bicuculline blocked the suppressive effect of systemically administered SKF 82958 on jaw movement activity.
CONCLUSIONS: These data suggest that the antiparkinsonian actions of SKF 82958 may be due to stimulation of D1 receptors in the ventrolateral striatum and substantia nigra pars reticulata. In addition, these results indicate that GABA mechanisms in the substantia nigra pars reticulata may be important for the antiparkinsonian effects of D1 agonists.
ESTHER : Mayorga_1999_Psychopharmacology.(Berl)_143_72
PubMedSearch : Mayorga_1999_Psychopharmacology.(Berl)_143_72
PubMedID: 10227082

Title : The role of ventrolateral striatal acetylcholine in the production of tacrine-induced jaw movements - Cousins_1999_Pharmacol.Biochem.Behav_62_439
Author(s) : Cousins MS , Finn M , Trevitt J , Carriero DL , Conlan A , Salamone JD
Ref : Pharmacol Biochem Behav , 62 :439 , 1999
Abstract : The anticholinesterase tacrine induces tremulous jaw movements in rats, and considerable evidence indicates that this response is dependent upon ventrolateral striatal mechanisms. Three experiments were conducted to study the relation between ventrolateral striatal acetylcholine and the production of tremulous jaw movements. In Experiment 1, intracranial microinjection of the acetylcholine synthesis inhibitor hemicholinium-3 into the ventrolateral neostriatum reduced tremulous jaw movements induced by 5.0 mg/kg tacrine. Microinjection of hemicholinium into a cortical site dorsal to striatum (Experiment 2) was without significant effect upon tacrine-induced tremulous jaw movements. In Experiment 3, rats were implanted with dialysis probes in the ventrolateral striatum to measure extracellular levels of acetylcholine during tacrine-induced jaw movements. Tacrine (2.5-5.0 mg/kg) increased both extracellular acetylcholine and tremulous jaw movements. The 5.0 mg/kg dose of tacrine produced a substantial increase in ventrolateral striatal acetylcholine levels (324% of baseline within 30 min). Across all tacrine-treated rats there was a significant linear correlation between tremulous jaw movements and acetylcholine levels (r = +0.56) during the first 30-min postinjection period. This correlation was largely due to the group that received 5.0 mg/kg tacrine; within this group, there was a very high correlation (r = +0.87) between tremulous jaw movements and acetylcholine levels in the first sample after injection. These data are consistent with the notion that tremulous jaw movements induced by tacrine are mediated by ventrolateral striatal acetylcholine. Moreover, these results suggest that dialysis methods could be used to monitor the relation between striatal acetylcholine and tremulous movements induced by a variety of different conditions.
ESTHER : Cousins_1999_Pharmacol.Biochem.Behav_62_439
PubMedSearch : Cousins_1999_Pharmacol.Biochem.Behav_62_439
PubMedID: 10080235

Title : Effects of subchronic administration of clozapine, thioridazine and haloperidol on tests related to extrapyramidal motor function in the rat - Trevitt_1998_Psychopharmacology.(Berl)_137_61
Author(s) : Trevitt J , Atherton A , Aberman J , Salamone JD
Ref : Psychopharmacology (Berl) , 137 :61 , 1998
Abstract : Clozapine, thioridazine (THIO) and haloperidol were administered for 14 consecutive days, and separate groups of rats were used to study the effects of these drugs on tremulous jaw movements and lever pressing. Rats were observed on day 13 for the ability of the antipsychotic drugs to induce jaw movements. Haloperidol produced a dose-related increase in jaw movements, while clozapine and THIO failed to induce jaw movements. On day 14, rats were challenged with 5.0 mg/kg of the anticholinesterase tacrine, which induces a very high level of jaw movement activity. Clozapine significantly reduced tacrine-induced tremulous jaw movements, while haloperidol did not. Although previous work had shown that acute THIO could suppress jaw movements, repeated THIO failed to do so. In order to provide an additional behavioral test for comparisons of the relative potencies of the antipsychotic drugs, rats were tested for the effects of these drugs on fixed ratio 5 lever pressing. All three drugs significantly suppressed lever pressing. Haloperidol showed sensitization with repeated injections, while clozapine showed tolerance. Data were analyzed by taking the ratio of the ED50 for suppression of tacrine-induced jaw movement over the ED50 for suppression of lever pressing on day 14. Clozapine reduced tacrine-induced jaw movements in a dose range slightly lower than that required for reduction of lever pressing. In contrast, THIO and haloperidol failed to affect tacrine-induced jaw movements even at doses that were 5-18 times the ED50 for suppression of lever pressing. Thus, tests of jaw movement activity and lever pressing after repeated administration may be useful for assessing atypical antipsychotic drugs.
ESTHER : Trevitt_1998_Psychopharmacology.(Berl)_137_61
PubMedSearch : Trevitt_1998_Psychopharmacology.(Berl)_137_61
PubMedID: 9631957

Title : Tremulous jaw movements in rats: a model of parkinsonian tremor - Salamone_1998_Prog.Neurobiol_56_591
Author(s) : Salamone JD , Mayorga AJ , Trevitt JT , Cousins MS , Conlan A , Nawab A
Ref : Prog Neurobiol , 56 :591 , 1998
Abstract : Several pharmacological and neurochemical conditions in rats induce 'vacuous' or 'tremulous' jaw movements. Although the clinical significance of these movements has been a subject of some debate, considerable evidence indicates that the non-directed, chewing-like movements induced by cholinomimetics, dopamine antagonists and dopamine depletions have many of the characteristics of parkinsonian tremor. These movements occur within the 3-7 Hz peak frequency range that is characteristic of parkinsonian tremor. Tremulous jaw movements are induced by many of the conditions that are associated with parkinsonism, and suppressed by several different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, amantadine and clozapine. Striatal cholinergic and dopaminergic mechanisms are involved in the generation of tremulous jaw movements, and substantia nigra pars reticulata appears to be a major basal ganglia output region through which the jaw movements are regulated. Future research on the neurochemical and anatomical characteristics of tremulous jaw movements could yield important insights into the brain mechanisms that generate tremulous movements.
ESTHER : Salamone_1998_Prog.Neurobiol_56_591
PubMedSearch : Salamone_1998_Prog.Neurobiol_56_591
PubMedID: 9871939

Title : Behavioral and electromyographic characterization of the local frequency of tacrine-induced tremulous jaw movements - Cousins_1998_Physiol.Behav_64_153
Author(s) : Cousins MS , Atherton A , Salamone JD
Ref : Physiol Behav , 64 :153 , 1998
Abstract : Rats were implanted with fine-wire electromyograph (EMG) electrodes and were videotaped to identify the local frequency characteristics and muscle activity associated with tacrine-induced tremulous jaw movements. All rats received intraperitoneal injections of 2.5 mg/kg tacrine. The videotape sessions were played back in slow motion (i.e., one-sixth normal speed), and an observer entered each jaw movement into a computer program that recalculated the interresponse time and the local frequency (in hertz) for each movement within a burst. Analyses of the distribution of frequencies showed that the peak frequency of jaw movements was in the 3- to 5-Hz frequency range, with an average frequency of 4.0 Hz. EMG electrodes were implanted into three jaw muscles: temporalis, anterior belly of digastricus, and masseter. Tremulous jaw movements were not accompanied by consistent changes in masseter activity. The anterior belly of digastricus showed bursts of EMG activity during some jaw movements, although the temporal relation between jaw movements and EMG activity was somewhat inconsistent. The muscle that showed activity most closely related to tremulous jaw movements was the temporalis. During bursts of jaw movements, temporalis muscles across several different rats showed bursts of EMG activity. Sections of videotape corresponding to bursts of EMG activity were reanalyzed by freeze-frame examination of the tape; typically, the temporalis showed a burst for each jaw movement, with the burst of activity occurring during the jaw-closing phase and the transition between jaw closing and opening. These results indicate that the local frequency of tremulous jaw movements is within the 3- to 7-Hz frequency that is typically associated with parkinsonian tremor. Moreover, the EMG data suggest that temporalis is a major contributor to the muscle activity that underlies tremulous jaw movements.
ESTHER : Cousins_1998_Physiol.Behav_64_153
PubMedSearch : Cousins_1998_Physiol.Behav_64_153
PubMedID: 9662079

Title : Tremulous characteristics of the vacuous jaw movements induced by pilocarpine and ventrolateral striatal dopamine depletions - Finn_1997_Pharmacol.Biochem.Behav_57_243
Author(s) : Finn M , Jassen A , Baskin P , Salamone JD
Ref : Pharmacol Biochem Behav , 57 :243 , 1997
Abstract : Vacuous jaw movements induced by the muscarinic agonist pilocarpine and striatal dopamine depletions were examined using a slow motion videotape system. With this procedure, rats were videotaped in a Plexiglas tube so that the profile of the head region could be seen. Vacuous jaw movements were analyzed by examining the tape at 1/6 normal speed. An observer recorded each jaw movement using a computer, and the computer program re-calculated the temporal characteristics of jaw movement responses back to normal speed. The interresponse time was recorded for each jaw movement, and each jaw movement interresponse time was assigned to a 50 ms wide time bin. Thus, the distribution of interresponse times could be used to analyze the temporal characteristics of jaw movement responses. In the first experiment, rats were administered saline vehicle, 1.0 mg/kg and 2.0 mg/kg pilocarpine. The rats were videotaped 10-15 min after injection, and the data were analyzed as described above. Pilocarpine induced very high levels of vacuous jaw movements, and the vast majority of all movements occurred in "bursts" with interresponse times of 1.0 s or less. Analysis of the interresponse time distributions showed that most of the jaw movements were within the 150-350 ms range. The modal jaw movement interresponse time was in the 150-200 ms range, which corresponds to a local frequency of 5-6.66 Hz. In the second experiment, the neurotoxic agent 6-hydroxydopamine was injected directly into the ventrolateral striatum in order to produce a local dopamine depletion. The dopamine-depleted rats were observed for jaw movements 7 days after surgery. The overall level of jaw movement activity resulting from dopamine-depletion was much lower than that produced by pilocarpine. There was a significant inverse correlation between ventrolateral striatal dopamine levels and total number of vacuous jaw movements. Videotape analysis indicated that the temporal characteristics of jaw movements induced by dopamine depletions were similar to those shown with pilocarpine. These experiments indicate that vacuous jaw movements induced by pilocarpine and striatal dopamine depletion occur in a frequency range similar to that shown in parkinsonian tremor.
ESTHER : Finn_1997_Pharmacol.Biochem.Behav_57_243
PubMedSearch : Finn_1997_Pharmacol.Biochem.Behav_57_243
PubMedID: 9164578

Title : Motor dysfunction produced by tacrine administration in rats - Carriero_1997_Pharmacol.Biochem.Behav_58_851
Author(s) : Carriero DL , Outslay G , Mayorga AJ , Aberman J , Gianutsos G , Salamone JD
Ref : Pharmacol Biochem Behav , 58 :851 , 1997
Abstract : In the present study, three experiments were conducted to provide a characterization of some of the motor effects of the anticholinesterase tacrine (1.25-5.0 mg/kg I.P.) in rats. In the first experiment, tacrine was found to produce tremulous jaw movements in the dose range of 1.25-5.0 mg/kg. The second experiment examined the effects of tacrine on locomotion, and it was demonstrated that tacrine produced a dose-related suppression of open-field motor activity. In the third experiment, the effects of tacrine were assessed using operant conditioning procedures. Behavioral output during lever pressing on a fixed ratio 5 schedule was recorded by a computerized system that measured response initiation time (time from offset of one response to onset of the next) and duration for each lever press. Tacrine administration substantially depressed lever pressing response rate. This deficit was largely due to a substantial increase in the average response initiation time. Analysis of the distribution of response initiation times indicated that tacrine-treated rats made relatively few responses with fast initiation times (e.g., 0-125 ms), and also that tacrine led to a dramatic increase in the number of pauses in responding (i.e., response initiation times greater than 2.5 s). Tacrine-treated rats showed a slight increase in the average initiation time for fast responses (i.e., a slight decrease in the local rate of responding), and also showed a substantial increase in the average length of pauses greater than 2.5 s. Analysis of response durations indicated that there was an overall increase in average response duration among animals that received the higher doses of tacrine. Although tacrine-induced decreases in the local rate of responding and increases in response duration contribute to the overall deficit, the major reason why tacrine-treated animals responded less was because they took much longer breaks in responding. It is possible that the tacrine-induced increases in pausing reflect a drug-induced akinesia. Thus, the present experiments indicate that tacrine impairs several aspects of motor function in the dose range tested. In view of the fact that tremor and motor slowing are classic symptoms of Parkinsonism, the present results in rats are consistent with the human literature indicating that tacrine (Cognex) can produce Parkinsonian side effects. Studies of the motor dysfunctions produced by tacrine in rats could be useful for investigating the motor side effects of tacrine in humans.
ESTHER : Carriero_1997_Pharmacol.Biochem.Behav_58_851
PubMedSearch : Carriero_1997_Pharmacol.Biochem.Behav_58_851
PubMedID: 9408186

Title : Tremulous jaw movements produced by acute tacrine administration: possible relation to parkinsonian side effects - Mayorga_1997_Pharmacol.Biochem.Behav_56_273
Author(s) : Mayorga AJ , Carriero DL , Cousins MS , Gianutsos G , Salamone JD
Ref : Pharmacol Biochem Behav , 56 :273 , 1997
Abstract : Previous work has shown that cholinomimetic drugs induce "vacuous" or non-directed jaw movements in rats. In the present study, five experiments were conducted to provide a pharmacological, anatomical and behavioral characterization of tacrine-induced vacuous jaw movements. In the first experiment, tacrine produced vacuous chewing in a dose-related manner in a range of 1.25 mg/kg to 1.0 mg/kg. This effect was reduced, also in a dose-related manner, by the co-administration of the muscarinic antagonist scopolamine in a range of 0.125 to 1.0 mg/kg, but not by N-methylscopolamine. The fourth experiment examined the effect of scopolamine (2.5 to 10.0 micrograms) injected into the ventrolateral striatum on vacuous jaw movements induced by 5.0 mg/kg tacrine. Intrastriatal injections of scopolamine completely blocked tacrine-induced jaw movements. The fifth experiment utilized a slow-motion videotaping system to analyze the temporal characteristics of vacuous chewing induced by 5.0 mg/kg tacrine. The vast majority of the movements occurred in rapid "bursts," and analysis of interresponse times (i.e., the time between each jaw movement) showed that most of the jaw movements occurred within a local frequency range of 3 to 7 Hz. Thus, tacrine-induced jaw movements are reduced by antimuscarinic treatment, and most of these movements occur in the parkinsonian tremor frequency range. Tremulous jaw movements induced by tacrine in rats appear to share some characteristics with Parkinsonian tremor.
ESTHER : Mayorga_1997_Pharmacol.Biochem.Behav_56_273
PubMedSearch : Mayorga_1997_Pharmacol.Biochem.Behav_56_273
PubMedID: 9050085

Title : Involvement of pallidal and nigral GABA mechanisms in the generation of tremulous jaw movements in rats - Finn_1997_Neurosci_80_535
Author(s) : Finn M , Mayorga AJ , Conlan A , Salamone JD
Ref : Neuroscience , 80 :535 , 1997
Abstract : Four experiments were conducted to investigate the role of pallidal and nigral GABA in the generation of tremulous jaw movements in rats. In these experiments, tremulous jaw movements were induced by i.p. injections of the anticholinesterase tacrine (5.0 mg/kg). Previous work has shown that the tremulous jaw movements induced by cholinomimetics and dopamine depletion are dependent upon striatal mechanisms. Thus, the present study investigated potential striatal output pathways that could be involved in the generation of these movements. Because there are GABAergic projections from neostriatum to entopeduncular nucleus (medial globus pallidus) and substantia nigra pars reticulata, the GABA agonist muscimol was injected directly into these structures to study the effects of GABA stimulation on tacrine-induced jaw movements. Injections of muscimol into the entopeduncular nucleus (25-100 ng) failed to have any significant effects on tacrine-induced vacuous jaw movements. However, injections of muscimol (12.5-50 ng) into the substantia nigra pars reticulata blocked the jaw movements induced by tacrine. In the third experiment, it was again demonstrated that 25.0 ng of muscimol injected directly into the substantia nigra pars reticulata blocked the jaw movements induced by tacrine; in addition, it was shown that injections of this dose 2.0 mm dorsal to the substantia nigra pars reticulata failed to affect tacrine-induced tremulous jaw movements. It was shown in the fourth experiment that injections of muscimol into a more medial portion of the substantia nigra pars reticulata also reduced tacrine-induced tremulous jaw movements. These results indicate that stimulation of GABA(A) receptors in substantia nigra pars reticulata can block tacrine-induced tremulous jaw movements. This finding is consistent with the notion that striatonigral GABA projections are involved in the generation of tremulous jaw movements. It is also possible that striatonigral GABA mechanisms are involved in human clinical phenomena such as parkinsonian tremor.
ESTHER : Finn_1997_Neurosci_80_535
PubMedSearch : Finn_1997_Neurosci_80_535
PubMedID: 9284355

Title : Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: effects of antiparkinsonian drugs - Cousins_1997_Eur.J.Pharmacol_322_137
Author(s) : Cousins MS , Carriero DL , Salamone JD
Ref : European Journal of Pharmacology , 322 :137 , 1997
Abstract : Several experiments were conducted to study the effects of established or potential antiparkinsonian drugs on the tremulous jaw movements induced by the anticholinesterase tacrine (9-amino-1,2,3,4-tetrahydroaminoacridine hydrochloride). In the first group of four experiments, separate groups of animals that received 2.5 or 5.0 mg/kg tacrine showed a dose-dependent decrease in tremulous jaw movements following co-administration of the non-selective dopamine receptor agonist apomorphine, the full dopamine D2 receptor agonist bromocriptine, and the full dopamine D1 receptor agonist APB (R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). Co-administration of the partial dopamine D1 receptor agonist SKF 38393 (R(+)-2,3,4,5-tetrahydro-7,8-dihydroxy-l phenyl-1 H-benzazepine: 7.5-30.0 mg/kg) did not reduce tremulous jaw movements produced by 2.5 or 5.0 mg/kg tacrine. In animals treated with 2.5 mg/kg tacrine, co-administration of SKF 38393 resulted in a dose-related trend towards a potentiation of tremulous jaw movements. In the second group of experiments, all rats received 2.5 mg/kg tacrine. The dopamine precursor L-DOPA (L-3,4-dihydroxyphenylalanine), the dopamine and norepinephrine releasing agent amantadine, and the muscarinic receptor antagonist benztropine all reduced tremulous jaw movements induced by 2.5 mg/kg tacrine. Across all experiments, it was noted that apomorphine, bromocriptine and benztropine were more potent than amantadine and L-DOPA. These results are broadly consistent with the therapeutic doses of these agents noted in the clinical literature. The results of these experiments indicate that tremulous jaw movements in rats may be a useful model for evaluating potential antiparkinsonian agents.
ESTHER : Cousins_1997_Eur.J.Pharmacol_322_137
PubMedSearch : Cousins_1997_Eur.J.Pharmacol_322_137
PubMedID: 9098680

Title : Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function - Trevitt_1997_Psychopharmacology.(Berl)_132_74
Author(s) : Trevitt JT , Lyons M , Aberman J , Carriero D , Finn M , Salamone JD
Ref : Psychopharmacology (Berl) , 132 :74 , 1997
Abstract : Evidence indicates that the antipsychotic drug clozapine has a low propensity for the induction of extrapyramidal motor symptoms, and also that clozapine has therapeutic effects in patients with idiopathic Parkinson's disease. Because tacrine-induced tremulous jaw movements in rats have been suggested as a possible model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the present work was undertaken to investigate the effects of clozapine on tremulous jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to determine the relative potency of this effect compared to other behavioral effects of clozapine, suppression of lever pressing was also studied. Clozapine reduced lever pressing in a dose-related manner, with an ED50 of approximately 5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the doses required for suppression of lever pressing. In contrast, the typical antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50 for suppression of lever pressing with that drug. Thioridazine and risperidone also suppressed tremulous jaw movements in roughly the same dose range at which lever pressing was reduced. It is possible that the suppression of tacrine-induced tremulous jaw movements by clozapine in rats is related to the unique behavioral and motor effects of clozapine. The ratio of potencies of these effects (i.e., suppression of tremulous jaw movements versus suppression of lever pressing) could be used as a behavioral procedure for assessing clozapine-like activity in novel compounds.
ESTHER : Trevitt_1997_Psychopharmacology.(Berl)_132_74
PubMedSearch : Trevitt_1997_Psychopharmacology.(Berl)_132_74
PubMedID: 9272762

Title : Effects of acute and repeated clozapine injections on cholinomimetic-induced vacuous jaw movements - Chesler_1996_Pharmacol.Biochem.Behav_54_619
Author(s) : Chesler EJ , Salamone JD
Ref : Pharmacol Biochem Behav , 54 :619 , 1996
Abstract : Three studies were undertaken to investigate the effects of the atypical neuroleptic clozapine on the vacuous jaw movements induced by cholinergic stimulation in rats. In the first experiment, acute clozapine injections (4.0-16.0 mg/kg) produced a dose-related suppression of the vacuous jaw movements induced by 0.4 mg/kg physostigmine. In the second experiment, acute injections of clozapine (2.0-16.0 mg/kg) also suppressed vacuous jaw movements induced by 4.0 mg/kg pilocarpine in a dose-related manner. The third experiment was designed to compare the effects of acute and repeated administration of 16.0 mg/kg clozapine. In this experiment, there were three groups: one that received 4.0 mg/kg pilocarpine, a second group that received pilocarpine plus an acute injection of 16.0 mg/kg clozapine, and a third group that received injections of 16.0 mg/kg clozapine for 14 consecutive days, including the final day in which they also were injected with pilocarpine. For the third experiment, animals were assessed for the sedative effects of clozapine as well as vacuous jaw movements. The results indicated that either acute or repeated injections of 16.0 mg/kg clozapine reduced vacuous jaw movements relative to rats that received pilocarpine alone, and the two clozapine-treated groups did not differ from each other. The sedation ratings indicated that acute injections of 16.0 mg/kg clozapine produced substantial drowsiness and sedation, whereas rats that had received clozapine for 14 days did not show substantial sedation. These results indicate that clozapine can suppress cholinomimetic-induced vacuous jaw movements. The suppressive effects of clozapine on pilocarpine-induced vacuous jaw movements do not show tolerance within the 14-day period of repeated injections, whereas the sedative effects of clozapine do show tolerance. Thus, these results demonstrate that the suppression of pilocarpine-induced vacuous jaw movements by clozapine is not merely an artifact of clozapine-induced sedation. Because pilocarpine-induced vacuous jaw movements share some characteristics with human parkinsonian symptoms, the present results are consistent with previous reports indicating that repeated injections of clozapine produce anti-parkinsonian effects.
ESTHER : Chesler_1996_Pharmacol.Biochem.Behav_54_619
PubMedSearch : Chesler_1996_Pharmacol.Biochem.Behav_54_619
PubMedID: 8743638

Title : Pharmacological characterization of performance on a concurrent lever pressing\/feeding choice procedure: effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs - Cousins_1994_Psychopharmacology.(Berl)_116_529
Author(s) : Cousins MS , Wei W , Salamone JD
Ref : Psychopharmacology (Berl) , 116 :529 , 1994
Abstract : This experiment was undertaken to provide a pharmacological characterization of performance on a task involving food-related instrumental and consummatory behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or approaching and consuming a less-preferred food (Lab Chow). The lever pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever pressing schedule. Previous work has shown that injection of dopamine (DA) antagonists, or depletion of DA in the nucleus accumbens, caused a substantial shift in behavior such that lever pressing was reduced but chow consumption increased. In the present study it was shown that the DA antagonist haloperidol decreased lever pressing and increased chow consumption at doses of 0.1 and 0.15 mg/kg. The D1 antagonist SCH 23390 (0.05, 0.1 and 0.15 mg/kg) and the non-selective DA antagonist cis-flupenthixol (0.3 and 0.45 mg/kg) decreased lever pressing and produced substantial increases in chow consumption. The D2 antagonist sulpiride decreased lever pressing, but produced only slight increases in chow intake at the highest dose. Pentobarbital reduced lever pressing and increased chow consumption at 10.0 mg/kg. The muscarinic agonist pilocarpine produced dose-related decreases in lever pressing, but failed to increase chow consumption. Amphetamine produced dose-related decreases in both lever pressing and chow consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Cousins_1994_Psychopharmacology.(Berl)_116_529
PubMedSearch : Cousins_1994_Psychopharmacology.(Berl)_116_529
PubMedID: 7701059

Title : Repeated scopolamine injections sensitize rats to pilocarpine-induced vacuous jaw movements and enhance striatal muscarinic receptor binding - Baskin_1994_Pharmacol.Biochem.Behav_49_437
Author(s) : Baskin PP , Gianutsos G , Salamone JD
Ref : Pharmacol Biochem Behav , 49 :437 , 1994
Abstract : This experiment was conducted to determine if repeated administration of the muscarinic antagonist scopolamine could increase pilocarpine-induced vacuous jaw movements and also enhance muscarinic receptor binding. Rats received daily injections of either scopolamine (0.5 mg/kg IP) or saline for 14 days. On day 15 rats received no injections of scopolamine, but did receive injections of pilocarpine (1.0, 2.0 or 4.0 mg/kg IP) or saline. After administration of pilocarpine or saline, all rats were observed for vacuous jaw movements and rearing behavior. The day after pilocarpine injections, rats were sacrificed and samples of tissue from the lateral neostriatum were removed to assess muscarinic receptor binding using 3H-QNB as the ligand. Analyses of the vacuous jaw movement data indicated that there was a significant dose-related increase in vacuous jaw movements induced by pilocarpine, and also that there was a significant enhancement of pilocarpine-induced vacuous jaw movements in rats pretreated with repeated scopolamine injections. There was not a significant scopolamine x pilocarpine interaction, suggesting that pretreatment with scopolamine produced an apparent parallel shift in the pilocarpine dose-response curve. Pilocarpine significantly suppressed rearing behavior, and scopolamine pretreatment significantly enhanced the suppression of rearing produced by pilocarpine. Analysis of the receptor binding data indicated that there was a significant increase in the number of muscarinic receptor sites (Bmax) in rats that received repeated scopolamine injections as compared to saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Baskin_1994_Pharmacol.Biochem.Behav_49_437
PubMedSearch : Baskin_1994_Pharmacol.Biochem.Behav_49_437
PubMedID: 7824562

Title : Vacuous jaw movements induced by sub-chronic administration of haloperidol: interactions with scopolamine - Steinpreis_1993_Psychopharmacology.(Berl)_111_99
Author(s) : Steinpreis RE , Baskin P , Salamone JD
Ref : Psychopharmacology (Berl) , 111 :99 , 1993
Abstract : The present series of experiments was conducted to investigate the vacuous jaw movements induced by sub-chronic administration of haloperidol (HP). In the first experiment, daily injection of 0.4 mg/kg HP for 10 days increased vacuous jaw movements and decreased rearing behavior. The second and third experiments investigated the interaction between the effects of HP and the anticholinergic drug scopolamine. Co-administration of 0.5 mg/kg scopolamine with 0.4 mg/kg HP for 9 days reduced vacuous jaw movements and increased rearing responses relative to rats that received HP alone. Co-administration of HP with 0.25 mg/kg scopolamine for 9 days increased rearing relative to rats that received HP alone, but there was no effect of the lower dose of scopolamine on vacuous jaw movements. Administration of 0.5 mg/kg scopolamine plus 0.4 mg/kg HP on days 11-14 to rats that had received HP alone for 10 days reversed the effect of HP on rearing, but not on vacuous jaw movements. Rats that had received HP plus scopolamine for 10 days showed dramatic increases in vacuous jaw movements when scopolamine was withdrawn. Because vacuous jaw movements are produced within the first few days of administration, reduced by administration of scopolamine, and exacerbated by withdrawal of scopolamine, the pharmacological characteristics of these movements do not appear to bear a close relation to those of tardive dyskinesia in humans. The present results are consistent with the hypothesis that vacuous jaw movements in rats share some characteristics with Parkinsonian symptoms.
ESTHER : Steinpreis_1993_Psychopharmacology.(Berl)_111_99
PubMedSearch : Steinpreis_1993_Psychopharmacology.(Berl)_111_99
PubMedID: 7870941

Title : Lateral striatal cholinergic mechanisms involved in oral motor activities in the rat - Salamone_1990_Psychopharmacology.(Berl)_102_529
Author(s) : Salamone JD , Johnson CJ , McCullough LD , Steinpreis RE
Ref : Psychopharmacology (Berl) , 102 :529 , 1990
Abstract : These experiments were undertaken to determine if local injection of pilocarpine in the neostriatum of the rat produces oral motor activities that are similar to those produced by systemic administration. In the first experiment, IP administration of 2.0-8.0 mg/kg pilocarpine increased chewing movements and tongue protrusions. In the second experiment, chronic guide cannulae were implanted bilaterally in ventromedial or ventrolateral striatum, and rats were injected with saline, 30, and 60 micrograms pilocarpine (per side). A dose-related increase in vacuous chewing was induced by injections of pilocarpine in the ventrolateral but not the ventromedial striatum. Tongue protrusions were induced by injections of pilocarpine into the ventromedial and the ventrolateral striatum. A third experiment demonstrated that this response was blocked completely by 10 micrograms scopolamine co-administered via the same cannulae, but the response was not reduced significantly by 10 micrograms haloperidol. These results indicate that ventrolateral striatal cholinergic mechanisms are involved in oral motor activities in the rat. This syndrome may provide a model for human clinical phenomena such as parkinsonian tremor.
ESTHER : Salamone_1990_Psychopharmacology.(Berl)_102_529
PubMedSearch : Salamone_1990_Psychopharmacology.(Berl)_102_529
PubMedID: 2096410

Title : Transplantation of embryonic ventral forebrain grafts to the neocortex of rats with bilateral lesions of nucleus basalis magnocellularis ameliorates a lesion-induced deficit in spatial memory - Welner_1988_Brain.Res_463_192
Author(s) : Welner SA , Dunnett SB , Salamone JD , MacLean B , Iversen SD
Ref : Brain Research , 463 :192 , 1988
Abstract : Embryonic ventral forebrain grafts containing developing cholinergic cells were transplanted to the neocortex of rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis. A lesion-induced deficit on performance of a spatial alternation test of memory was reduced by such transplants. When the same animals were treated with the acetylcholinesterase inhibitor physostigmine (0.05 mg/kg), however, performance on the behavioral task was not further promoted, and therefore, under these conditions, the cholinergic cortical transplants appear not to be subject to modulation by anticholinesterase drugs.
ESTHER : Welner_1988_Brain.Res_463_192
PubMedSearch : Welner_1988_Brain.Res_463_192
PubMedID: 3058269

Title : Synthesis and characterization of all four isomers of the muscarinic agonist 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] - Saunders_1987_J.Med.Chem_30_969
Author(s) : Saunders J , Showell GA , Baker R , Freedman SB , Hill D , McKnight A , Newberry N , Salamone JD , Hirshfield J , Springer JP
Ref : Journal of Medicinal Chemistry , 30 :969 , 1987
Abstract : The four separated isomers of the muscarinic agonist 1, previously known as AF30, have been synthesized by a route that has allowed the absolute stereochemistry of each isomer to be assigned. With the chirality of (-)-camphanic acid known, X-ray analysis of the more crystalline intermediate diastereomeric camphanate 5A allowed the absolute stereochemistry at the quinuclidine chiral center to be determined. Each diastereomer was separately transformed into the spirodioxolane with concomitant introduction of the second chiral center. Chromatographic separation followed by a second crystal structure determination revealed the absolute stereochemistry of all four isomers of 1. Detailed biological evaluation of each isomer indicated that while the 3(R),2'(S) isomer was the most active in binding studies, it was the 3(R),2'(R) isomer that displayed the largest functional selectivity between ganglion (M-1 site) and heart (M-2 site). With the same internal chiral standard, the absolute configuration of the more active enantiomer of 3 was shown to be S, confirming earlier literature reports.
ESTHER : Saunders_1987_J.Med.Chem_30_969
PubMedSearch : Saunders_1987_J.Med.Chem_30_969
PubMedID: 3585909

Title : Behavioural and pharmacological characterization of the mouth movements induced by muscarinic agonists in the rat - Salamone_1986_Psychopharmacology.(Berl)_88_467
Author(s) : Salamone JD , Lalies MD , Channell SL , Iversen SD
Ref : Psychopharmacology (Berl) , 88 :467 , 1986
Abstract : Pilocarpine administered in doses of 1.25-10.0 mg/kg (IP) produced a variety of mouth movements in the rat. The most frequent of these movements was a chewing behaviour, which increased up to a mean frequency of over 40 per min at the highest doses. Tongue protrusion and gaping also showed dose-dependent increases. Yawning tended to increase in some doses, though these increases were not significant, and yawning was relatively infrequent. Pre-treatment with scopolamine reduced these responses, while pre-treatment with methyl scopolamine did not. Injections of oxotremorine or arecoline, but not carbachol, produced dose-related increases in mouth movements similar to those produced by pilocarpine. These results suggest that mouth movements in the rat are caused by stimulation of central muscarinic receptors. This may prove to be an important behavioural sign of central cholinomimetic activity.
ESTHER : Salamone_1986_Psychopharmacology.(Berl)_88_467
PubMedSearch : Salamone_1986_Psychopharmacology.(Berl)_88_467
PubMedID: 3085134

Title : Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats - Salamone_1984_Behav.Brain.Res_13_63
Author(s) : Salamone JD , Beart PM , Alpert JE , Iversen SD
Ref : Behavioural Brain Research , 13 :63 , 1984
Abstract : Rats were trained on a reinforced alternation paradigm using an elevated T-maze. After pre-surgical training subjects received either ibotenic acid (4 micrograms/0.4 microliter) or vehicle (pH 7.4, 0.4 microliter) bilaterally into the region of the nucleus basalis magnocellularis--an important source of neocortical acetylcholine projections. Acetylcholinesterase staining of sectioned brains revealed a loss of neocortical, but not hippocampal staining in lesioned animals. On the T-maze task, lesioned rats showed significantly impaired choice performance relative to controls. They also demonstrated significant side biases, the degree of which was correlated with choice performance deficit.
ESTHER : Salamone_1984_Behav.Brain.Res_13_63
PubMedSearch : Salamone_1984_Behav.Brain.Res_13_63
PubMedID: 6541050