Intrastriatal infusion of lisuride--a potential treatment for Parkinson's disease? Behavioral and autoradiographic studies in 6-OHDA lesioned rats.

Abstract

The present study examined the effect of chronic intrastriatal infusion of the dopamine receptor agonist lisuride on apomorphine-induced rotational behaviour and on D2-dopamine receptors in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. The completeness of the lesion of the right ascending nigrostriatal dopaminergic pathway was confirmed by apomorphine-induced rotation and [3H]-mazindol autoradiography. The intrastriatal infusion of lisuride (0.5 microgram/h) into the lesioned striatum for 2 weeks induced an immediate but temporary spontaneous contralateral rotation and a reduction of apomorphine-induced rotation of 47.2% relative to pre-lisuride infusion. The density of D2-receptors in the lisuride-infused striatum was significantly decreased by 40% relative to vehicle-infused 6-OHDA lesioned rats. The level of D2-dopamine receptors returned to normal levels 3 weeks after the termination of lisuride infusion. These results show that the intrastriatal infusion of lisuride reverses the behavioural and D2-dopamine receptor changes present in the 6-OHDA lesion rat model of Parkinson's disease.