Memantine, but not dizocilpine, ameliorates cognitive deficits in adult rats withdrawn from chronic ingestion of alcohol.
Adult rats were given a 20% ethanol solution as their only source of fluid for 6 months and then withdrawn from alcohol. During the first 4 weeks of the withdrawal period, animals were intraperitoneally injected with either memantine (20 mg/kg bolus followed by 1 mg/kg every 12 h) or dizocilpine (MK-801; 0.1 mg/kg every 12 h), both of which are antagonists of N-methyl-D-aspartate receptors. Ten weeks after initiation of the withdrawal procedure, cognitive status of animals was assessed using the Morris water maze. Withdrawal from alcohol produced robust deficits in the performance of rats on the acquisition task and on the probe trial. Treatment with memantine resulted in a complete reversal of these behavioral impairments. In contrast, treatment with MK-801 was found to be ineffective in preventing cognitive alterations associated with chronic alcohol consumption and withdrawal.
Lukoyanov
N V
NV
Department of Anatomy, Porto Medical School, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. luk@med.up.pt
Paula-Barbosa
M M
MM
D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008559:Memantine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate; D008559:Memantine