Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies

Abstract

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.

FOS expression induced by an ethanol-paired conditioned stimulus

“…One possibility is that acute ethanol exposure may have suppressed expression of the conditioned increase in FOS in those brain areas. This explanation seems quite plausible for the two hippocampal areas in light of previous studies showing that ethanol has a general suppressive effect on FOS expression in hippocampus (Ryabinin, 1998). However, as noted earlier (Section 4.1), it is also possible that the apparent conditioned increases in FOS observed in saline tested mice were caused by a novelty response to omission of the expected ethanol injection.…”

“…The finding of conditioned FOS increases in hippocampus (CA1, CA3, DG) in Experiment 2 was somewhat surprising given that acute ethanol exposure has previously been shown either to have no effect (Ryabinin and Wang, 1998) or to reduce FOS expression (Ryabinin, 1998) in hippocampus. Nevertheless, the finding of ethanol-induced conditioned increases in the hippocampus appears to be consistent with previous reports of increased FOS in hippocampal areas of rats exposed to an environment in which they had previously self-administered ethanol (CA3: Topple et al, 1998) or cocaine (CA1, DG: Neisewander et al, 2000).…”

Ethanol, 3,4-Methylenedioxymethamphetamine (Ecstasy) and Their Combination: Long-Term Behavioral, Neurochemical and Neuropharmacological Effects in the Rat

“…Acutely, ethanol alters memory (eg Givens, 1995), motor coordination (eg Gallate et al, 2003; but see Metz et al, 2003), and anxiety-related behaviors (eg Gallate et al, 2003;Langen et al, 2002;Ryabinin, 1998). Beside hyperlocomotion and hyperthermia, MDMA alters motor coordination (Marston et al, 1999), anxiety (Bhattacharya et al, 1998;Morley and McGregor, 2000;Sumnall et al, 2004), and cognitive functions (Braida et al, 2002;Ho et al, 2004;Marston et al, 1999; but see Ricaurte et al, 1993).…”

Ethanol-responsive genes: identification of transcription factors and their role in metabolomics

“…[1][2][3] These effects are mediated by alcohol's effect on the expression of a large number of genes. [4][5][6][7][8] We have established that alcohol causes altered expression of genes belonging to a number of cellular pathways including stress response, ethanol metabolism, protein modification, gene regulation and cell signaling.…”