HIPPOCAMPUS IN DELAY EYEBLINK CLASSICAL-CONDITIONING - ESSENTIAL FOR NEFIRACETAM AMELIORATION OF LEARNING IN OLDER RABBITS

Rabbits acquire conditioned responses (CRs) normally with bilateral re moval of the hippocampus, but alterations of the intact hippocampus ca n affect the rate of acquisition. The cognition-enhancing drug, nefira cetam ameliorated the acquisition of CRs in older rabbits, protected m embrane dysfunction in hippocampal CA1 neurons following oxygen and gl ucose deprivation, and promoted the release of diverse neurotransmitte rs, including acetylcholine. Because the septo-hippocampal cholinergic system is demonstrated to be involved in eyeblink conditioning, this experiment was undertaken to explore whether nefiracetam ameliorates c onditioning via the hippocampus. Data from 53 rabbits of a mean age of 28 months were tested under two drug conditions (10 or 0 mg/kg nefira cetam) and 4 lesion conditions (bilateral hippocampectomy, bilateral n eocortical removal, sham surgery, no surgery). The three groups of nef iracetam-treated rabbits with intact hippocampus acquired CRs more rap idly than the vehicle-treated groups, but rabbits with bilateral hippo campectomy treated with nefiracetam learned like vehicle-treated rabbi ts. Results suggest that nefiracetam ameliorates learning via the hipp ocampus. Because of the parallels between conditioning in rabbits with disrupted hippocampal cholinergic systems and conditioning in Alzheim er's disease (AD), these results suggest that nefiracetam may ameliora te conditioning in AD as it ameliorates conditioning in older rabbits.