Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies.
Acute alcohol intoxication disrupts memory acquisition in humans and laboratory animals. This review summarizes recent behavioral and immediate early gene expression studies addressing the mechanisms of this phenomenon. Most behavioral investigations agree that the amnestic effect of alcohol is due to its preferential detrimental effect on hippocampus-dependent than on hippocampus-independent forms of learning. However, some hippocampal lesion studies contradict these results. Learning in behavioral paradigms is accompanied by induction of c-fos and other immediate early genes in many brain regions of the animal. In contrast, studies on alcohol-mediated changes in expression of this gene confirm selective hippocampal suppression of basal and experience-induced expression of c-fos after acute and repeated administration of alcohol. This hippocampal suppression is in marked contrast with alcohol-mediated induction of c-fos expression in other brain areas. However, the selective suppression of hippocampal gene expression and memory by alcohol is most likely mediated by a number of interacting neurotransmitter systems. Thus, effects of lower doses of alcohol (0.5 g/kg or lower in rats) seem to be preferentially mediated through GABAergic systems. At intermediate doses (0.75-2 g/kg), several other neurotransmitter systems are affected besides GABA. Higher doses lead to none-specific effects, probably involving even more neurotransmitter systems. Elucidation of these neurotransmitter systems will be highly important for developing rational approaches for correction of alcohol-related cognitive disorders.
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health Sciences University, 97201, USA.
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D000425:Alcohol Amnestic Disorder / Q000503:physiopathology; D000435:Alcoholic Intoxication / Q000503:physiopathology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced; D051381:Rats
D000431:Ethanol