Moss DE

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Full name : Moss Donald E

First name : Donald E

Mail : Laboratory of Psychobiochemistry, University of Texas at El Paso

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Country : USA

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Website : \/\/academics.utep.edu\/Default.aspx?alias=academics.utep.edu\/dmoss-phd

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References (14)

Title : Anti-neurodegenerative benefits of acetylcholinesterase inhibitors in Alzheimer's disease: Nexus of cholinergic and nerve growth factor dysfunction - Moss_2021_Curr.Alzheimer.Res__
Author(s) : Moss DE , Perez RG
Ref : Curr Alzheimer Res , : , 2021
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is increasingly viewed as a complex multi-dimensional disease without effective treatments. Recent randomized, placebo-controlled studies have shown volume losses of ~0.7% and ~3.5% per year, respectively, in the basal cholinergic forebrain (CBF) and hippocampus in untreated suspected prodromal AD. One year of donepezil treatment reduced these annualized rates of atrophy to about half of untreated rates. Similar positive although variable results have also been found in volumetric measurements of the cortex and whole brain in patients with mild cognitive impairment as well as more advanced AD stages after treatments with all three currently available acetylcholinesterase (AChE) inhibitors (donepezil, rivastigmine, and galantamine). Here we review the anti-neurodegenerative benefits of AChE inhibitors and the expected parallel disease-accelerating impairments caused by anticholinergics, within a framework of the cholinergic hypothesis of AD and AD-associated loss of nerve growth factor (NGF). Consistent with the "loss of trophic factor hypothesis of AD," we propose that AChE inhibitors enhance acetylcholine-dependent release and uptake of NGF, thereby sustaining cholinergic neuronal viability and thus lowing AD-associated degeneration of the CBF, to delay dementia progression ultimately. We propose that improved cholinergic therapies for AD started early in asymptomatic persons, especially those with risk factors, will delay the onset, progression, or emergence of dementia. The currently available competitive pseudo-irreversible AChE inhibitors are not CNS-selective and thus induce gastrointestinal toxicity that limits cortical AChE inhibition to ~30% (ranges from 19% to 41%) as measured by in vivo PET studies in patients undergoing therapy. These levels of inhibition are marginal about what is required for effective symptomatic treatment of dementia or slowing AD-associated neurodegeneration. In contrast, because of the inherently slow de novo synthesis of AChE in the CNS (about one-tenth the rate of synthesis in peripheral tissues), irreversible AChE inhibitors produce significantly higher levels of inhibition in the CNS than in peripheral tissues. Such an irreversible inhibitor produces ~68% CNS AChE inhibition in patients undergoing therapy and ~80% inhibition in cortical biopsies of non-human primates. The full therapeutic benefits of AChE inhibitors, whether for symptomatic treatment of dementia or disease-slowing, thus would benefit by producing high levels of CNS inhibition. One way to obtain such higher levels of CNS AChE inhibition would be by using irreversible inhibitors.
ESTHER : Moss_2021_Curr.Alzheimer.Res__
PubMedSearch : Moss_2021_Curr.Alzheimer.Res__
PubMedID: 34911424

Title : Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer's Disease: Are Irreversible Inhibitors the Future? - Moss_2020_Int.J.Mol.Sci_21_
Author(s) : Moss DE
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Decades of research have produced no effective method to prevent, delay the onset, or slow the progression of Alzheimer's disease (AD). In contrast to these failures, acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors slow the clinical progression of the disease and randomized, placebo-controlled trials in prodromal and mild to moderate AD patients have shown AChE inhibitor anti-neurodegenerative benefits in the cortex, hippocampus, and basal forebrain. CNS neurodegeneration and atrophy are now recognized as biomarkers of AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria and recent evidence shows that these markers are among the earliest signs of prodromal AD, before the appearance of amyloid. The current AChE inhibitors (donepezil, rivastigmine, and galantamine) have short-acting mechanisms of action that result in dose-limiting toxicity and inadequate efficacy. Irreversible AChE inhibitors, with a long-acting mechanism of action, are inherently CNS selective and can more than double CNS AChE inhibition possible with short-acting inhibitors. Irreversible AChE inhibitors open the door to high-level CNS AChE inhibition and improved anti-neurodegenerative benefits that may be an important part of future treatments to more effectively prevent, delay the onset, or slow the progression of AD.
ESTHER : Moss_2020_Int.J.Mol.Sci_21_
PubMedSearch : Moss_2020_Int.J.Mol.Sci_21_
PubMedID: 32414155

Title : Is Combining an Anticholinergic with a Cholinesterase Inhibitor a Good Strategy for High-Level CNS Cholinesterase Inhibition? - Moss_2019_J.Alzheimers.Dis_71_1099
Author(s) : Moss DE
Ref : J Alzheimers Dis , 71 :1099 , 2019
Abstract : The currently approved cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) produce gastrointestinal toxicity which limits dosing to that which produces only about 25% to 35% CNS cholinesterase inhibition in Alzheimer's disease patients undergoing treatment, below the minimum therapeutic target of about 40% to 50% CNS inhibition considered necessary to treat cognitive impairment. A recent strategy for producing high-level CNS acetylcholinesterase (AChE) inhibition (50% or higher) is to co-administer a muscarinic anticholinergic with the AChE inhibitor to block the dose-limiting cholinergic overstimulation of the gastrointestinal system, allow more robust AChE inhibition in the CNS, and improve efficacy in the treatment of Alzheimer's disease. Unfortunately, most common muscarinic anticholinergics, including solifenacin, readily penetrate the CNS and are directly associated with long-term exacerbation of the underlying neuropathology of Alzheimer's disease and increased brain atrophy. The co-administration of an anticholinergic with an AChE inhibitor is a rational strategy for improving efficacy in the symptomatic treatment of dementia, but there are significant long-term risks that have not yet been considered. For long-term safety against accelerating the underlying disease processes in Alzheimer's disease, anticholinergics used to increase the tolerability of AChE inhibitors should not penetrate, or have very limited penetration, of the blood-brain barrier. Neurotrophic-mediated mechanisms by which cholinergic drugs may affect neurodegeneration in Alzheimer's disease are explored and improved treatment options are suggested.
ESTHER : Moss_2019_J.Alzheimers.Dis_71_1099
PubMedSearch : Moss_2019_J.Alzheimers.Dis_71_1099
PubMedID: 31476160

Title : Cholinesterase Inhibitor Therapy in Alzheimer's Disease: The Limits and Tolerability of Irreversible CNS-Selective Acetylcholinesterase Inhibition in Primates - Moss_2017_J.Alzheimers.Dis_55_1285
Author(s) : Moss DE , Perez RG , Kobayashi H
Ref : J Alzheimers Dis , 55 :1285 , 2017
Abstract : Irreversible acetylcholinesterase (AChE) inhibition accumulates to high levels in the central nervous system (CNS) because AChE turnover in the brain is much slower than in peripheral tissues. As expected from this CNS selectivity, the irreversible AChE inhibitor methanesulfonyl fluoride (MSF) produces significant cognitive improvement in Alzheimer's disease patients without the gastrointestinal toxicity that plagues other AChE inhibitors. However, without dose-limiting gastrointestinal toxicity, one shortcoming of the prior human studies of MSF is that the upper limits of CNS AChE inhibition that might be tolerated could not be tested. Therefore, in this study, monkeys were treated with escalating intramuscular (IM) doses of MSF that culminated with several weeks of 1.5 mg/kg dosing, more than eight times the prior human clinical dose, still without signs of toxicity. Brain biopsies showed that approximately 80% AChE inhibition had been produced and that the new synthesis of cortical AChE had a half-time (t1/2) of approximately 12 days. A single IM dose of 1.5 mg/kg MSF produced approximately 59% inhibition in cerebrospinal fluid (CSF) AChE as measured one day later. This corresponds to a peak of approximately 80% inhibition in CSF AChE at the time of the injection, recovering with a t1/2 of 2.4 days. Computational analyses suggest that MSF at clinically relevant doses could theoretically produce a steady-state AChE inhibition between 65% and 85% in the CNS. These data suggest that the full therapeutic advantage of AChE inhibition therapy can be realized without interference from dose-limiting gastrointestinal toxicity if an irreversible inhibitor is employed.
ESTHER : Moss_2017_J.Alzheimers.Dis_55_1285
PubMedSearch : Moss_2017_J.Alzheimers.Dis_55_1285
PubMedID: 27858711

Title : Cholinergic Transmission during Nicotine Withdrawal Is Influenced by Age and Pre-Exposure to Nicotine: Implications for Teenage Smoking - Carcoba_2014_Dev.Neurosci_36_347
Author(s) : Carcoba LM , Orfila JE , Natividad LA , Torres OV , Pipkin JA , Ferree PL , Castaneda E , Moss DE , O'Dell LE
Ref : Developmental Neuroscience , 36 :347 , 2014
Abstract : Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naive adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During nicotine withdrawal, ACh levels in the NAc were increased in a similar manner in adolescent versus adult rats. However, the increase in ACh that was observed in adult rats experiencing nicotine withdrawal was blunted in pre-exposed adults. These neurochemical effects do not appear to be related to nicotine metabolism, as plasma cotinine levels were similar across all groups. The second study revealed that nicotine exposure increased AChE activity in the NAc to a greater extent in adolescent versus adult rats. There was no difference in AChE activity in pre-exposed versus naive adult rats. In conclusion, our results suggest that nicotine exposure during adolescence enhances baseline ACh in the NAc. However, the finding that ACh levels were similar during withdrawal in adolescent and adult rats suggests that the enhanced vulnerability to tobacco use during adolescence is not related to age differences in withdrawal-induced increases in cholinergic transmission. Our results also suggest that exposure to nicotine during adolescence suppresses withdrawal-induced increases in cholinergic responses during withdrawal. Taken together, this report illustrates important short- and long-term changes within cholinergic systems that may contribute to the enhanced susceptibility to tobacco use during adolescence. (c) 2014 S. Karger AG, Basel.
ESTHER : Carcoba_2014_Dev.Neurosci_36_347
PubMedSearch : Carcoba_2014_Dev.Neurosci_36_347
PubMedID: 24854235

Title : A randomized phase I study of methanesulfonyl fluoride, an irreversible cholinesterase inhibitor, for the treatment of Alzheimer's disease - Moss_2013_Br.J.Clin.Pharmacol_75_1231
Author(s) : Moss DE , Fariello RG , Sahlmann J , Sumaya I , Pericle F , Braglia E
Ref : British Journal of Clinical Pharmacology , 75 :1231 , 2013
Abstract : AIMS: To ascertain the tolerability profile of single and repeated oral doses of methanesulfonyl fluoride (MSF, SNX-001) in healthy aged subjects, and to determine the degree of erythrocyte acetylcholinesterase (AChE) inhibition induced by MSF after single and repeated oral doses.
METHODS: To calculate properly the kinetics and the duration of AChE inhibition, the effects of MSF were also studied in rodents. These experiments suggested that MSF administered three times per week should provide safe and efficacious AChE inhibition. In a randomized placebo-controlled phase I study, 3.6 mg, 7.2 mg or 10.8 mg MSF were then orally administered to 27 consenting healthy volunteers (aged 50 to 72 years). After a single dose phase and a 1 week wash-out period, the subjects received the same doses three times per week for 2 weeks.
RESULTS: Twenty-two out of the 27 subjects completed the study. Four patients withdrew due to adverse events (AEs) and one for non-compliance. Erythrocyte AChE was inhibited by a total of 33%, 46%, and 62% after 2 weeks of 3.6 mg, 7.2 mg and 10.8 mg MSF, respectively. No serious AEs occurred. The most frequent AEs were headache (27%), nausea (11%) and diarrhoea (8%).
CONCLUSIONS: MSF proved to be well tolerated even with repeated oral dosing. It is estimated that MSF provided a degree of AChE inhibition that should effectively enhance memory. This molecule deserves to be tested for efficacy in a pilot randomized controlled study in patients with Alzheimer's disease.
ESTHER : Moss_2013_Br.J.Clin.Pharmacol_75_1231
PubMedSearch : Moss_2013_Br.J.Clin.Pharmacol_75_1231
PubMedID: 23116458

Title : In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat - Carcoba_2008_Pharmacol.Biochem.Behav_88_374
Author(s) : Carcoba LM , Santiago M , Moss DE , Cabeza R
Ref : Pharmacol Biochem Behav , 88 :374 , 2008
Abstract : There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure.
ESTHER : Carcoba_2008_Pharmacol.Biochem.Behav_88_374
PubMedSearch : Carcoba_2008_Pharmacol.Biochem.Behav_88_374
PubMedID: 17920111

Title : Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats - Borlongan_2005_Brain.Res_1038_50
Author(s) : Borlongan CV , Sumaya IC , Moss DE
Ref : Brain Research , 1038 :50 , 2005
Abstract : Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 +/- 10%) and significantly prolonged acquisition (398 +/- 62 s) and shortened retention (79 +/- 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 +/- 8%), they performed significantly better in the passive avoidance task (255 +/- 36 s and 145 +/- 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task.
ESTHER : Borlongan_2005_Brain.Res_1038_50
PubMedSearch : Borlongan_2005_Brain.Res_1038_50
PubMedID: 15748872

Title : Prenatal exposure to the acetylcholinesterase inhibitor methanesulfonyl fluoride alters forebrain morphology and gene expression - Byers_2005_Brain.Res.Dev.Brain.Res_158_13
Author(s) : Byers DM , Irwin LN , Moss DE , Sumaya IC , Hohmann CF
Ref : Brain Research Developmental Brain Research , 158 :13 , 2005
Abstract : Methanesulfonyl fluoride (MSF) is a CNS-selective acetylcholinesterase (AChE) inhibitor, currently being developed and tested for the treatment of symptoms of Alzheimer's disease. We have previously confirmed that a single in utero exposure to MSF at clinically appropriate doses inhibits AChE activity in fetal rat brain by 20%, and when administered throughout gestation, MSF achieves a 40% level of inhibition. Here, we show that rats chronically exposed in utero to MSF display marked sex-specific differences in morphological development of the cerebral cortical layers compared with controls at 7 days of age. Forebrain size and cortical thickness were increased in females and decreased in males. An analysis of gene expression in neonate brain on the day of birth revealed sex-specific differential expression of over 25 genes, including choline acetyltransferase (ChAT), which were affected by prenatal MSF exposure. Many of these genes are associated with sexual differentiation and brain development, while others are involved in more generalized cellular and metabolic processes. The changes observed in cortical morphology and gene expression suggest a critical developmental role for AChE in the fetal nervous system, most likely through its effect on cholinergic neurotransmission.
ESTHER : Byers_2005_Brain.Res.Dev.Brain.Res_158_13
PubMedSearch : Byers_2005_Brain.Res.Dev.Brain.Res_158_13
PubMedID: 15964079

Title : Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of safety and efficacy in the treatment of senile dementia of the Alzheimer type - Moss_1999_Alzheimer.Dis.Assoc.Disord_13_20
Author(s) : Moss DE , Berlanga P , Hagan MM , Sandoval H , Ishida C
Ref : Alzheimer Disease & Associated Disorders , 13 :20 , 1999
Abstract : The purpose of the present study was to evaluate methanesulfonyl fluoride (MSF), a very long-acting CNS-selective acetylcholinesterase (AChE) inhibitor, as a palliative treatment for senile dementia of the Alzheimer type (SDAT). In experiment I, MSF (0.03-0.18 mg/kg) was administered orally to 10 normal volunteers to measure toxicity and establish dose/response function in erythrocyte AChE. MSF produced a dose-response function of %inhibition = (40)(Log10[MSF mg/kg] + 51.7) with no toxicity at these doses. Experiment II was a 16-week double-blind, placebo-controlled study of the safety and efficacy of MSF in doses of up to 0.18 mg/kg given three times per week in 5 men and 10 women (60-82 years), with Mini-Mental State Examination (MMSE) scores of 9-24, who had SDAT. MSF produced a mean of 89.5% inhibition of erythrocyte AChE in patients and improved cognitive performance as measured by the MMSE, Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-COG), Global Deterioration Scale, and the Clinical Interview Based Impression of Change (CIBIC). Most of the improvement on the ADAS-COG was maintained 8 weeks after ending MSF. No patients left the study because of drug-related adverse events and there were no toxic effects. MSF may be a safe and effective palliative treatment for SDAT and further clinical trials in larger groups of patients are warranted.
ESTHER : Moss_1999_Alzheimer.Dis.Assoc.Disord_13_20
PubMedSearch : Moss_1999_Alzheimer.Dis.Assoc.Disord_13_20
PubMedID: 10192638

Title : Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease: selectivity toward human brain acetylcholinesterase compared with butyrylcholinesterase - Pacheco_1995_J.Pharmacol.Exp.Ther_274_767
Author(s) : Pacheco G , Palacios-Esquivel R , Moss DE
Ref : Journal of Pharmacology & Experimental Therapeutics , 274 :767 , 1995
Abstract : One consistent finding in senile dementia of the Alzheimer's type is that the brain has reduced ability to synthesize acetylcholine. This has been related, in part, to memory dysfunctions. Although a cholinergic deficit is not singularly responsible for symptoms of dementia, treatment strategies have been designed to facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To minimize toxicity, however, a cholinesterase inhibitor selective for only AChE would be an ideal treatment. The purpose of this study was to determine the selectivity of physostigmine, metrifonate, methanesulfonyl fluoride and tetrahydroaminoacridine (tacrine) toward AChE as compared with butyrylcholinesterase (BChE) in human cortex. The results show that methanesulfonyl fluoride is selective as an inhibitor of AChE as compared with BChE. Physostigmine inhibited AChE more than BChE. Metrifonate was found to inhibit BChE more than AChE. Tetrahydroaminoacridine inhibited both enzymes in a complex way.
ESTHER : Pacheco_1995_J.Pharmacol.Exp.Ther_274_767
PubMedSearch : Pacheco_1995_J.Pharmacol.Exp.Ther_274_767
PubMedID: 7636741

Title : Methanesulfonyl fluoride (MSF) blocks scopolamine-induced amnesia in rats - Palacios-Esquivel_1993_Neurobiol.Aging_14_93
Author(s) : Palacios-Esquivel RL , Pacheco G , Moss DE
Ref : Neurobiology of Aging , 14 :93 , 1993
Abstract : Cholinesterase inhibitors, such as physostigmine and tetrahydroaminoacridine, have been found to alleviate some of the memory deficits characteristic of senile dementia of the Alzheimer's type (SDAT). Many toxic side effects, however, have been associated with the use of these compounds. Recently, a cholinesterase inhibitor, methanesulfonyl fluoride (MSF), was discovered to have low toxicity, central nervous system (CNS) selectivity, and a long therapeutic duration. The purpose of this research was to determine if MSF (1.5 mg/kg) would be effective in reducing or blocking amnesia induced by various doses of scopolamine (0.2, 0.6, and 2.0 mg/kg). One hundred and twenty-two female Sprague-Dawley albino rats were trained and retention tested in a Y-maze brightness discrimination task. MSF was highly effective in reducing scopolamine-induced amnesia.
ESTHER : Palacios-Esquivel_1993_Neurobiol.Aging_14_93
PubMedSearch : Palacios-Esquivel_1993_Neurobiol.Aging_14_93
PubMedID: 8450938

Title : Chronic methanesulfonyl fluoride enhances one-trial per day reward learning in aged rats - Malin_1993_Neurobiol.Aging_14_393
Author(s) : Malin DH , Plotner RE , Radulescu SJ , Ferebee RN , Lake JR , Negrete PG , Schaefer PJ , Crothers MK , Moss DE
Ref : Neurobiology of Aging , 14 :393 , 1993
Abstract : Aged (24-month-old) rats were treated chronically with methanesulfonyl fluoride (MSF), an acetylcholinesterase (AChE) inhibitor with selectivity for central nervous system AChE, or with injection vehicle alone. Twelve 0.22 mg/kg IP injections were given over 4 weeks. MSF rats showed significantly greater speed and accuracy on a 1 trial/day discriminative reward learning task. The chronic MSF treatment resulted in a 56% decrease in brain AChE activity but no discernable locomotor side effects and no liver damage as indicated by aspartate transferase activity.
ESTHER : Malin_1993_Neurobiol.Aging_14_393
PubMedSearch : Malin_1993_Neurobiol.Aging_14_393
PubMedID: 8367021

Title : Review of cholinergic mechanisms and memory -
Author(s) : Moss DE , Deutsch JA
Ref : Cholinergic.Mechanisms, Raven Press :483 , 1975
PubMedID: