Necessity of the hippocampus for alcohol's indirect but not direct behavioral action

Many of the behavioral actions of ethyl alcohol are mimicked by hippocampal lesions. With the present study, we begin to assess the extent to which alcohol's behavioral effects are actually mediated by the hippocampus. Using an appetitive runway task, the direct (pharmacological) and indirect (variously referred to as stimulus, dissociative, or state-dependent) actions of alcohol (dose increments from 0.75 to 1.12 g/kg) were investigated in rats with hippocampal or sham lesions. Alcohol facilitated performance (running time) during acquisition in both lesion and sham-operated rats, suggesting that the direct effects of alcohol were not dependent upon hippocampal mediation. Indirect ethanol actions were assessed in a 2 × 2 × 2 design, where half of the animals experienced a change from the alcohol or vehicle state that prevailed during training. Sham-operated animals displayed the usual asymmetrical dissociation, but lesion rats did not. They exhibited only the direct effects of the drug. Besides indicating the necessity of the hippocampus for indirect alcohol actions, the pattern of results permitted interpretation of asymmetry as the differential summation of direct and indirect drug effects. Finally, in every case—lesion or drug, direct or indirect action—the changes in runway performance were directly attributable to changes in the frequency of exploration within the alley that competed with running time, the usual performance measure.