Characterization of muscarinic receptors modulating acetylcholine release in the rat neostriatum

Two classical and two nonclassical muscarinic agents were tested for their effects on neostriatal acetylcholine (ACh) release. The classical muscarinic antagonist, atropine (0.1-2 microM), increased ACh release in a dose-dependent fashion, whereas the 'nonclassical' antagonist, pirenzepine (2-200 microM), had no effect on ACh release. The muscarinic agonist, oxotremorine (1-100 microM), and its analog, oxotremorine-M (0.1-50 microM), both decreased ACh release in a dose-dependent fashion. The inhibitory potency of oxotremorine-M was approximately 20 times that of oxotremorine, and the inhibitory effects of both agonists were blocked by atropine. The results obtained with the muscarinic antagonists indicate that 'M-2 type' muscarinic receptors mediate ACh release in the neostriatum, but further pharmacological analyses are required to assign with certainty the receptor subtype involved in neostriatal ACh release.