Ed. Levin et al., WORKING-MEMORY PERFORMANCE AND CHOLINERGIC EFFECTS IN THE VENTRAL TEGMENTAL AREA AND SUBSTANTIA-NIGRA, Brain research, 657(1-2), 1994, pp. 165-170
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.