INVOLVEMENT OF CHOLINERGIC PRESYNAPTIC RECEPTORS OF NICOTINIC AND MUSCARINIC TYPES IN CONTROL OF SPONTANEOUS RELEASE OF DOPAMINE FROM STRIATAL DOPAMINERGIC TERMINALS IN RAT

Abstract

Rat striatal slices (2) were superfused continuously with L-3,5-3H tyrosine and 3H-dopamine (3H-DA) release was estimated in serial fractions of superfusates. The spontaneous release of 3H-DA was reduced by about 50% when slices were superfused with a Ca-free medium containing ethylene glycol bis (.beta.-aminoethyl ether)-N,N''-tetraacetic acid (EGTA) (10-4 M) or with a medium containing tetrodotoxin (5 .times. 10-7 M). These effects were not related to a change in 3H-DNA synthesis since the rate of L-3,5-3H tyrosine hydroxylation, as measured by 3H-H2O formation was not significantly reduced. Acetylcholine (ACh) (10-5 M) stimulated the release of 3H-DA (about 100%). This effect was abolished in the absence of Ca; it was partially blocked by pempidine (10-5 M), atropine (10-6 M) or scopolamine (10-5, 10-6 M). Oxotremorine (10-5 M) enhanced 3H-DA release but to a lesser extent (60%) than ACh (10-5 M); its action was completely blocked by atropine (10-6 M) and unaffected by pempidine (10-5 M). The ACh- (10-5 M) and oxotremorine- (10-5 M) stimulating effects on 3H-DA spontaneous release were still detected in slices superfused in the presence of tetrodotoxin (5 .times. 10-7 M). In the presence of the neurotoxin, the effect of ACh (10-5 M) was significantly reduced by pempidine (10-5 M) and the effect of oxotremorine (10-5 M) was blocked by atropine (10-6 M). The presence of cholinergic presynaptic receptors of the nicotinic and muscarinic types on striatal dopaminergic terminals was suggested.