Intrastriatal dopaminergic agents, muscarinic stimulation, and GABA antagonism compared for rotation responses in rats.

We tested the common hypothesis that rotation on systemic injection of dopaminergic agents in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra is attributable to unequal stimulation of dopamine receptors between the two striata. No rotation occurred when dopamine, apomorphine or amphetamine were injected into dorsal striatum or nucleus accumbens of intact, unanesthetized rats. Intrastriatal haloperidol elicited ipsiversive postural deviation only in conjunction with hypermotility induced by systemic amphetamine. In unilateral 6-hydroxydopamine-lesioned rats, intrastriatal apomorphine elicited rotation directed away from the side of its injection, whether intact or lesioned. Carbachol elicited short-latency rotation, contraversive to injection in dorsal striatum or nucleus accumbens, in both intact and 6-hydroxydopamine-lesioned rats. The rotation response to carbachol was suppressed by atropine administered systemically or into the site of intrastriatal carbachol. Picrotoxin or bicuculline produced contraversive rotation or contralateral myoclonic jerks on injection into the striatum in intact rats. The results show that asymmetric stimulation of striatal dopamine receptors is not sufficient to cause rotation, unless the receptors have been denervated. On the other hand, asymmetric stimulation muscarinic receptors is in itself enough to produce the imbalance of gamma-aminobutyric acid (GABA)ergic striatal outputs responsible for rotation.