WORKING-MEMORY PERFORMANCE AND CHOLINERGIC EFFECTS IN THE VENTRAL TEGMENTAL AREA AND SUBSTANTIA-NIGRA

The nicotinic antagonist mecamylamine has been found to impair working memory performance in the radial-arm maze (RAM) after s.c. or i.c.v. administration. Mecamylamine has important interactions with dopaminer gic (DA) systems. Mecamylamine-induced memory deficits in the RAM are potentiated by the D-2 antagonist raclopride and reversed by the D-2 a gonist quinpirole. The nicotinic agonist nicotine has been found to im prove working memory performance in the RAM after s.c. or i.c.v. admin istration. Nicotine-induced memory improvement in the RAM is potentiat ed by the D-2 agonist quinpirole. The midbrain DA nuclei, the substant ia nigra (SN) and the ventral tegmental area (VTA) have relatively den se concentrations of nicotinic receptors which may be critical sites o f action for mecamylamine and nicotine. In the current study, the effe cts of mecamylamine (1, 3.3 and 10 mu g/side) infusions into the SN (n = 12) and VTA (n = 13) on working memory in the radial-arm maze were examined in adult female Sprague-Dawley rats. The 10-mu g/side dose of mecamylamine significantly impaired radial-arm maze working memory pe rformance when infused into either the SN or VTA. No significant effec ts of mecamylamine on response latency were seen. The nicotinic agonis ts cytisine (0.1, 0.33 and 1.0 mu g/side) and nicotine (0.3, 1.0 and 3 .3 mu g/side) were administered in a counterbalanced order. The high d ose of cytisine (1 mu g/side) nearly caused a significant deficit in c hoice accuracy. Nicotine slightly depressed choice accuracy but not si gnificantly in this study. The interaction of nicotine and mecamylamin e was then studied. A dose of 1.0 mu g/side of nicotine caused a signi ficant decrease in choice accuracy. Interestingly, this was significan tly reversed by a 3.3-mu g/side dose of mecamylamine. Studies of the m uscarinic antagonist scopolamine (1, 3.3 and 10 mu g/side) and the mus carinic agonist pilocarpine (3, 10 and 30 mu g/side) did not detect si gnificant effects on RAM choice accuracy. These data support the invol vement of nicotinic innervation of the midbrain DA nuclei in memory fu nction.