Hippocampal-dependent learning and experience-dependent activation of the hippocampus are preferentially disrupted by ethanol.

A classical fear conditioning paradigm was used to examine the effect of acute ethanol on the acquisition of context conditioning, a hippocampal-dependent associative task, and tone conditioning, a hippocampal-independent task. Administration of ethanol before the presentation of seven tone-shock pairings severely disrupted the acquisition of context conditioning, but had only a slight effect on tone conditioning, when conditioned fear was measured 48 h later. This effect was dose dependent: a dose of 0.5 g/kg had no effect on either context or tone conditioning, while doses of 1.0 and 1.5 g/kg disrupted context conditioning by 78-86%, and tone conditioning by 9-17%. Subsequent experiments indicated that ethanol's preferential effect on context conditioning could not be attributed to the fact that context conditioning is weaker than tone conditioning, ethanol-induced changes in motivational state or state-dependent learning. The effect of ethanol on stimulus-induced increases in hippocampal and neocortical expression of c-fos mRNA, a marker for changes in metabolic neuronal activity, was also examined. Ethanol completely blocked the induction of hippocampal c-fos mRNA by exposure to the conditioning context alone or seven tone-shock pairings, but only attenuated neocortical responses to these stimuli. Together, these results suggest that ethanol disrupts hippocampal-dependent learning by preferentially impairing stimulus processing at the level of the hippocampus.