BASAL FOREBRAIN INJECTIONS OF THE BENZODIAZEPINE PARTIAL INVERSE AGONIST FG-7142 ENHANCE MEMORY OF RATS IN THE DOUBLE Y-MAZE

Cholinergic replacement strategies have achieved little success in the treatment of Alzheimer's disease. It has been suggested that the mnem onic function of cholinergic neurons may be enhanced by treatments tha t reduce GABA-ergic inhibition, while preserving the normal pattern of activity in the cholinergic neurons. Following on these suggestions, the present study investigated the mnemonic effects of intra-nucleus b asalis magnocellularis (NBM) injections of the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 714 2). Rats were surgically implanted with bilateral cannulae in the NBM prior to training in a double Y-maze. Daily training sessions continue d until reference and working memory choice performance stabilized to a criterion of greater than or equal to 91% correct. Rats (n = 9) rece ived FG 7142 bilaterally in doses of 0.2, 2.0 and 3.0 mu g/0.5 mu l pe r side, muscimol (a GABA(A) agonist) in a dose of 0.1 mu g/0.5 mu l pe r side, vehicle (345 mu g 2-hydroxypropyl-beta-cyclodextrin/0.5 mu l s aline per side) or no injection in a counterbalanced order with retrai ning to criterion between treatments. Muscimol impaired choice accurac y on both the reference and working memory components, but the effect was bigger for working memory, replicating our previous findings. Two doses of FG 7142 (0.2 and 2.0 mu g/0.5 mu l) enhanced choice accuracy on the working memory component. The present results suggest that benz odiazepine partial inverse agonists may enhance mnemonic function.