title: Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats.
abstract: Central cholinergic dysfunction contributes to acute spatial memory deficits produced by ethanol administration. Donepezil and rivastigmine elevate acetylcholine levels in the synaptic cleft through the inhibition of cholinesterases-enzymes involved in acetylcholine degradation. The aim of our study was to reveal whether donepezil (acetylcholinesterase inhibitor) and rivastigmine (also butyrylcholinesterase inhibitor) attenuate spatial memory impairment as induced by acute ethanol administration in the Barnes maze task (primary latency and number of errors in finding the escape box) in rats. Additionally, we compared the influence of these drugs on ethanol-disturbed memory. In the first experiment, the dose of ethanol (1.75 g/kg, i.p.) was selected that impaired spatial memory, but did not induce motor impairment. Next, we studied the influence of donepezil (1 and 3 mg/kg, i.p.), as well as rivastigmine (0.5 and 1 mg/kg, i.p.), given either before the probe trial or the reversal learning on ethanol-induced memory impairment. Our study demonstrated that these drugs, when given before the probe trial, were equally effective in attenuating ethanol-induced impairment in both test situations, whereas rivastigmine, at both doses (0.5 and 1 mg/kg, i.p.), and donepezil only at a higher dose (3 mg/kg, i.p.) given prior the reversal learning, attenuated the ethanol-induced impairment in cognitive flexibility. Thus, rivastigmine appears to exert more beneficial effect than donepezil in reversing ethanol-induced cognitive impairments-probably due to its wider spectrum of activity. In conclusion, the ethanol-induced spatial memory impairment may be attenuated by pharmacological manipulation of central cholinergic neurotransmission.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Gawel
authors.affiliation: Sahlgrenska University Hospital, 413 45, Göteborg, Sweden.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Labuz
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gibula-Bruzda
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jenda
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Marszalek-Grabska
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Filarowska
authors.affiliation: Department of Biochemistry and Neurobiology, AGH University of Science and Technology, Mickiewicza 30, 30-059, Krakow, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093, Lublin, Poland. jolka.kotlinska@umlub.pl.
authors.forename: Jolanta H
authors.initials: JH
authors.lastname: Kotlinska
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D007189:Indans / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017208:Rats, Wistar; D011930:Reaction Time; D000068836:Rivastigmine / Q000494:pharmacology*; D045442:Rotarod Performance Test; D065852:Spatial Memory / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000431:Ethanol; D000077265:Donepezil; D000068836:Rivastigmine
keywords: Barnes maze; Donepezil; Ethanol; Rivastigmine; Spatial memory