Bartolini L

References (10)

Title : Effect of subchronic treatment with metrifonate and tacrine on brain cholinergic function in aged F344 rats - Giovannini_1998_Eur.J.Pharmacol_354_17
Author(s) : Giovannini MG , Scali C , Bartolini L , Schmidt B , Pepeu G
Ref : European Journal of Pharmacology , 354 :17 , 1998
Abstract : The effects of 21-day treatment with the acetylcholinesterase inhibitors metrifonate (80 mg kg(-1) per os (p.o.)) and tacrine (3 mg kg(-1) p.o.), twice daily, on cortical and hippocampal cholinergic systems were investigated in aged rats (24-26 months). Extracellular acetylcholine levels were measured by transversal microdialysis in vivo; choline acetyltransferase and acetylcholinesterase activities were measured ex vivo by means of radiometric methods. Basal cortical and hippocampal extracellular acetylcholine levels, measured 18 h after the last metrifonate treatment, were about 15 and two folds higher, respectively, than in control and tacrine-treated rats. A challenge with metrifonate further increased cortical and hippocampal acetylcholine levels by about three and four times, respectively. Basal extracellular acetylcholine levels, measured 18 h after the last treatment with tacrine were not statistically different from those of the control rats. A challenge with tacrine increased cortical and hippocampal extracellular acetylcholine levels by about four and two times. A 75% inhibition of cholinesterase activity was found 18 h after the last metrifonate administration, while only a 15% inhibition was detectable 18 h after the last tacrine administration. The challenge with metrifonate or tacrine resulted in 90 and 80% cholinesterase inhibition, respectively. These results demonstrate that in aging rats a subchronic treatment with metrifonate results in a long-lasting, cholinesterase inhibition, and a persistent increase in acetylcholine extracellular levels which compensate for the age-associated cholinergic hypofunction. Metrifonate is therefore a potentially useful agent for the cholinergic deficit accompanying Alzheimer's disease.
ESTHER : Giovannini_1998_Eur.J.Pharmacol_354_17
PubMedSearch : Giovannini_1998_Eur.J.Pharmacol_354_17
PubMedID: 9726626

Title : Acetylcholine release from the frontal cortex during exploratory activity - Giovannini_1998_Brain.Res_784_218
Author(s) : Giovannini MG , Bartolini L , Kopf SR , Pepeu G
Ref : Brain Research , 784 :218 , 1998
Abstract : The activation of the cortical cholinergic system was investigated in 3- and 25-month-old male Wistar rats, by measuring by transversal microdialysis the changes in cortical extracellular acetylcholine (ACh) levels during the performance of simple spontaneous tasks involving exploratory activity and working memory. Two days after implantation of the microdialysis probe in the frontal cortex, object recognition was investigated by either moving the rats from the home cage to the arena containing the objects or keeping the rats in the arena and introducing the objects. Spontaneous alternation was investigated in a Y runway. Young rats discriminated between familiar and novel objects and alternated in the Y runway, while aged rats were unable to discriminate. Whenever rats were moved from the home cage to the arena, ACh release increased (+70-80%) during the exploratory activity. Handling per se had no effect on extracellular ACh levels. When young rats were left in the arena, introduction of the objects caused some exploratory activity and object recognition but no increase in ACh release. ACh release increased by about 300% during spontaneous alternation. In aging rats basal extracellular ACh levels and their increase after placement in the arena were less than half that in young rats. Our work demonstrates that a novel environment activates the cortical cholinergic system, which presumably is associated with arousal mechanisms and selective attentional functions. It also demonstrates that in aging rats the cortical cholinergic hypofunction is associated with a loss of non-spatial working memory.
ESTHER : Giovannini_1998_Brain.Res_784_218
PubMedSearch : Giovannini_1998_Brain.Res_784_218
PubMedID: 9518622

Title : Effect of metrifonate on extracellular brain acetylcholine and object recognition in aged rats - Scali_1997_Eur.J.Pharmacol_325_173
Author(s) : Scali C , Giovannini MG , Bartolini L , Prosperi C , Hinz V , Schmidt B , Pepeu G
Ref : European Journal of Pharmacology , 325 :173 , 1997
Abstract : The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats. Extracellular acetylcholine levels were measured by transversal microdialysis in vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old rats did not discriminate between familiar and novel objects. In old rats, metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase activity in the cortex and hippocampus, a 4-fold increase in extracellular acetylcholine levels in the cortex only, and restored object recognition. In young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral cortex and hippocampus, a 2-fold increase in cortical and hippocampal extracellular acetylcholine levels, and no effect on object recognition. The slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats had no effect on cortical acetylcholine levels and object recognition. In conclusion, metrifonate may improve the age-associated cholinergic hypofunction and cognitive impairment.
ESTHER : Scali_1997_Eur.J.Pharmacol_325_173
PubMedSearch : Scali_1997_Eur.J.Pharmacol_325_173
PubMedID: 9163564

Title : Tacrine administration enhances extracellular acetylcholine in vivo and restores the cognitive impairment in aged rats - Scali_1997_Pharmacol.Res_36_463
Author(s) : Scali C , Giovannini MG , Prosperi C , Bartolini L , Pepeu G
Ref : Pharmacol Res , 36 :463 , 1997
Abstract : The effect of oral tacrine administration on cortical and hippocampal extracellular acetylcholine (ACh) levels has been investigated by a microdialysis technique, coupled to a HPLC method, in 6- and 22-24-month-old rats. In order to assess whether the increase in extracellular ACh levels was associated with an improvement in the age-related cognitive impairment, the object recognition and step-trough passive avoidance tests were carried out in the treated rats. The extracellular ACh levels measured in the cortex and hippocampus of aged rats without cholinesterase inhibitor in the perfusion Ringer solution were 39 and 54% lower, respectively, than in the young rats. At the dose of 3 mg kg-1, tacrine brought about a three- to four-fold increase in extracellular ACh levels, both in young and aged rats, which peaked 60-80 min after administration and disappeared within the next 60 min. At the same dose, tacrine caused a twofold increase in extracellular ACh levels in the hippocampus of young rats and a sixfold increase in aged rats. The absolute ACh levels at the peak in aged rats were not significantly different from those of young rats. In the object recognition test, aging rats were unable to discriminate between the familiar and novel object. Discrimination was restored by the administration of tacrine at the dose of 1 and 3 mg kg-1, but not 0. 3 mg kg-1 given 30 min before the first trial. Tacrine (3 mg kg-1 p. o.) administered to aging rats before the training trial significantly improved the acquisition of the passive avoidance conditioned response. Our findings demonstrate that tacrine increased both cortical and hippocampal extracellular ACh levels and improved behavioural functions in aged rats.
ESTHER : Scali_1997_Pharmacol.Res_36_463
PubMedSearch : Scali_1997_Pharmacol.Res_36_463
PubMedID: 9446713

Title : Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats - Blandina_1996_Br.J.Pharmacol_119_1656
Author(s) : Blandina P , Giorgetti M , Bartolini L , Cecchi M , Timmerman H , Leurs R , Pepeu G , Giovannini MG
Ref : British Journal of Pharmacology , 119 :1656 , 1996
Abstract : 1. The effects of histamine and agents at histamine receptors on spontaneous and 100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving, rats, and on cognitive tests are described. 2. Local administration of histamine (0.1-100 microM) failed to affect spontaneous but inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01-10 microM) and immepip (0.01-10 microM) mimicked the effect of histamine. 3. Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor-induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7. These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.
ESTHER : Blandina_1996_Br.J.Pharmacol_119_1656
PubMedSearch : Blandina_1996_Br.J.Pharmacol_119_1656
PubMedID: 8982515

Title : Amyloid beta-peptides injection into the cholinergic nuclei: morphological, neurochemical and behavioral effects -
Author(s) : Pepeu G , Giovannelli L , Casamenti F , Scali C , Bartolini L
Ref : Prog Brain Res , 109 :273 , 1996
PubMedID: 9009716

Title : Differential effects of amyloid peptides beta-(1-40) and beta-(25-35) injections into the rat nucleus basalis - Giovannelli_1995_Neurosci_66_781
Author(s) : Giovannelli L , Casamenti F , Scali C , Bartolini L , Pepeu G
Ref : Neuroscience , 66 :781 , 1995
Abstract : The nucleus basalis of male Charles River Wistar rats was injected with 10 micrograms of the beta-amyloid peptides beta-(1-40) and beta-(25-35) and changes in the morphology of the lesioned area, the release of acetylcholine from the cortex, and in behavior were investigated. Injections of saline and a scrambled (25-35) peptide were used as controls. One week after lesioning, a Congo Red-positive deposit of aggregated material was found at the beta-peptides injection site, which lasted for about 21 days in the case of the beta-(25-35) peptide and at least two months for beta-(1-40). No deposit was detected after scrambled peptide injection. At one week post injection, an extensive glial reaction surrounded the injection site of all peptides and saline as well. Such a reaction was still present but rather attenuated after two months. A decrease in the number of cholinergic neurons was detected in the nucleus basalis after one week with all treatments except saline. After two months, a reduction in the number of choline acetyltransferase-immunopositive neurons was still detectable in the rats injected with beta-(1-40) but not in the beta-(25-35)-or scrambled-injected. The reduction in choline acetyltransferase immunoreactivity was closely paralleled by a decrease in basal acetylcholine release from the parietal cortex ipsilateral to the lesion. Disruption of object recognition was observed in the first weeks after beta-(25-35) peptide injection, whereas the beta-(1-40) peptide impaired the performance only two months after lesion. Rats with lesions induced by beta-peptides may be a useful animal model of amyloid deposition for investigation of the pathogenetic mechanisms leading to Alzheimer's disease.
ESTHER : Giovannelli_1995_Neurosci_66_781
PubMedSearch : Giovannelli_1995_Neurosci_66_781
PubMedID: 7651609

Title : Nerve growth factor increases extracellular acetylcholine levels in the parietal cortex and hippocampus of aged rats and restores object recognition - Scali_1994_Neurosci.Lett_170_117
Author(s) : Scali C , Casamenti F , Pazzagli M , Bartolini L , Pepeu G
Ref : Neuroscience Letters , 170 :117 , 1994
Abstract : Male Wistar rats (3- and 20-month-old) were perfused i.c.v. with 1.5 micrograms of either nerve growth factor (NGF) or cytochrome C daily for 14 days. At the end of the infusion, the object-recognition test was carried out and extracellular acetylcholine levels (ACh) were measured in the cortex and hippocampus by transversal microdialysis technique. In 20-month-old control rats, the cortical and hippocampal ACh levels were 35 and 45% lower, respectively, than in 3-month-old rats and the ability to discriminate between a familiar and new object was impared. In the old rats treated with NGF, the ACh release as well as the behavioral performance showed no difference from those of young rats. These findings indicate that both ACh levels and memory impairment are improved in aged rats by NGF treatment and suggest that there is a relationship between object recognition and the activity of the forebrain cholinergic system.
ESTHER : Scali_1994_Neurosci.Lett_170_117
PubMedSearch : Scali_1994_Neurosci.Lett_170_117
PubMedID: 8041485

Title : Long-term ethanol consumption by rats: effect on acetylcholine release in vivo, choline acetyltransferase activity, and behavior - Casamenti_1993_Neurosci_56_465
Author(s) : Casamenti F , Scali C , Vannucchi MG , Bartolini L , Pepeu G
Ref : Neuroscience , 56 :465 , 1993
Abstract : The extent and duration of cholinergic hypofunction induced by long-term ethanol consumption was investigated in the rat. Ethanol (20% v/v) was administered to male adult Wistar rats as a sole source of fluid for three or six months. Control rats received tap water. The body weight, food and fluid intake in ethanol-treated rats were lower than in control rats throughout the treatment. After three months of ethanol consumption, and one week withdrawal, acetylcholine release in freely moving rats, investigated by microdialysis technique coupled to high-performance liquid chromatography quantification, was significantly decreased by 57 and 32% in the hippocampus and cortex, respectively, while choline acetyltransferase activity was significantly decreased (-30%) only in the hippocampus. A complete recovery of choline acetyltransferase activity and acetylcholine release was found after four ethanol-free weeks. Conversely, after four weeks of withdrawal following six months of ethanol treatment, the recovery in acetylcholine release was not accompanied by that in choline acetyltransferase activity, which remained significantly lower than in control rats in both cortex and hippocampus. The ability of rats to negotiate active and passive avoidance conditioned response tasks, tested after four ethanol-free weeks, was strongly impaired in both three- and six-month ethanol-treated rats. In conclusion, our experiments demonstrate that the development of a long-lasting cholinergic hypofunction requires at least six months of ethanol administration. The hypofunction affects choline acetyltransferase activity and acetylcholine release differently, and undergoes a remarkable recovery.
ESTHER : Casamenti_1993_Neurosci_56_465
PubMedSearch : Casamenti_1993_Neurosci_56_465
PubMedID: 8247273

Title : Lesions of cholinergic forebrain nuclei: changes in avoidance behavior and scopolamine actions - Lo_1982_Pharmacol.Biochem.Behav_17_933
Author(s) : Lo Conte G , Bartolini L , Casamenti F , Marconcini-Pepeu I , Pepeu G
Ref : Pharmacol Biochem Behav , 17 :933 , 1982
Abstract : The acquisition of active (shuttle-box) and passive avoidance conditioned responses and the effects of scopolamine on acetylcholine (ACh) output in freely moving rats and on conditioned responses were investigated 20 days after placing a unilateral lesion in the magnocellular forebrain nuclei (MFN). In the lesioned rats spontaneous ACh output from the cerebral cortex ipsilateral to the lesion was slightly decreased, while on the other hand the increase in ACh output elicited by scopolamine was strongly reduced. Sham operated rats always performed more active avoidance responses than MFN lesioned rats in the daily training shuttle-box sessions, and the facilitating effect of scopolamine (1 mg/kg IP) on the shuttle-box performance was suppressed. However the lesion did not disrupt the shuttle-box performance whenever training had taken place before the lesion. In the lesioned rats retested 30 min after the training trial, an impairment of the passive avoidance response was found. The effect of the lesion was potentiated by scopolamine. The results show therefore that MFN lesions impair the cortical cholinergic mechanisms, whose activity seems to play an important role in cognitive functions.
ESTHER : Lo_1982_Pharmacol.Biochem.Behav_17_933
PubMedSearch : Lo_1982_Pharmacol.Biochem.Behav_17_933
PubMedID: 6294688