Pharmacological investigation on rotational behaviour induced by unilateral electrical stimulation of the substantia nigra in the rat

Abstract

In order to elucidate pharmacological properties of rotational behaviour produced by unilateral electrical stimulation of the substantia nigra, effects of 6-hydroxydopamine treatment, dopamine receptor antagonists and agonists were investigated in the rat. Dopamine and its metabolites in the striatum were estimated after the stimulation. Intranigral treatment of 6-hydroxydopamine remarkably inhibited rotational behaviour induced by electrical stimulation. Antipsychotic drugs, 1 mg/kg haloperidol i.p. and 1 mg/kg pimozide i.p., decreased the behaviour by 50% of the control level. Sulpiride and metoclopramide did not exert significant influences on the behaviour. The dopamine receptor agonist apomorphine, 0.5 and 1 mg/kg s.c., markedly suppressed the stimulation-induced rotation, although it produced stereotypy, i.e. sniffing and gnawing. Bromocriptine, 10 mg/kg i.p., also suppressed rotational behaviour and produced locomotor activation without electrical stimulation. Methamphetamine did not have significant effects on the behaviour. Unilateral electrical stimulation of the substantia nigra produced an increase in the content of dopamine metabolites in the ipsilateral striatum of the rat pretreated with probenecid. These results suggest that the nigrostriatal dopaminergic system plays an important role in rotational behaviour produced by the electrical stimulation, and dopamine receptor agonists suppress the behaviour through a stimulating effect on the presynaptic dopamine receptor.