Basal forebrain injections of the benzodiazepine partial inverse agonist FG 7142 enhance memory of rats in the double Y-maze

Abstract

Cholinergic replacement strategies have achieved little success in the treatment of Alzheimer's disease. It has been suggested that the mnemonic function of cholinergic neurons may be enhanced by treatments that 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 basalis magnocellularis (NBM) injections of the benzodiazepine receptor partial inverse agonist N-methyl-β-carboline-3-carboxamide (FG 7142). Rats were surgically implanted with bilateral cannulae in the NBM prior to training in a double Y-maze. Daily training sessions continued until reference and working memory choice performance stabilized to a criterion of - 91% correct. Rats ( n = 9) received FG 7142 bilaterally in doses of 0.2, 0.2 and 3.0 μg/0.5 μl per side, muscimol (a GABA A agonist) in a dose of 0.1 μg/0.5 μl per side, vehicle (345 μg 2-hydroxypropyl-β-cyclodextrin/0.5 μl saline per side) or no injection in a counterbalanced order with retraining to criterion between treatments. Muscimol impaired choice accuracy 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 μg/0.5 μl) enhanced choice accuracy on the working memory component. The present results suggest that benzodiazepine partial inverse agonists may enhance mnemonic function.