Effect of nicotinic and muscarinic drugs on amphetamine- and apomorphine-induced circling behaviour in rats.

Abstract

The effect of drugs modulating the activity of nicotinic or muscarinic cholinergic receptors on the circling behaviour induced by amphetamine and apomorphine in rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic pathway was studied. Nicotine (0.2 mg/kg subcutaneously) significantly increased amphetamine-induced circling behaviour and tended to inhibit apomorphine-induced circling behaviour. Mecamylamine and pempidine (both 2 mg/kg intraperitoneally) slightly but significantly depressed the intensity of circling behaviour induced by amphetamine, but failed to modify the induced by apomorphine. Pilocarpine (10 mg/kg intraperitoneally) clearly inhibited both amphetamine- and apomorphine-induced circling behaviour. Unlike pilocarpine, atropine (10 mg/kg intraperitoneally significantly increases the intensity of the circling behaviour induced by amphetamine and also to some extent that induced by apomorphine. Neither hexamethonium (5 mg/kg intraperitoneally) nor methylatropine (1 mg/kg subcutaneously) modified the circling behaviour induced by either amphetamine or apomorphine. The results show that stimulation of central nicotinic and muscarinic receptors may have some opposite effects on the dopamine dependent circling behaviour. The presynaptic nicotinic cholinergic receptors on the terminals of the nigrostriatal dopaminergic neurones, stimulation of which may increase the release of dopamine, might be involved in the action of nicotinic drugs. The muscarinic cholinergic receptors in the striatum and/or in the substantia nigra might be involved in the action of muscarinic drugs.