Topography of dopamine behaviours mediated by D1 and D2 receptors revealed by intrastriatal injection of SKF 38393, lisuride and apomorphine in rats with a unilateral 6-hydroxydopamine-induced lesion

Stereotaxic injections of a dopamine D1 receptor agonist (SKF 38393) into different regions of the supersensitive striatum of rats with a unilateral 6-hydroxydopamine-induced lesion duplicated the systemic effects of the drug in a topographical manner. Although there was considerable overlap, it was possible to recognize discrete active zones or "hot-spots" giving rise to prominent sniffing, head movements and contralaterally directed circling, posture and grooming, both in the coronal plane and along the rostro-caudal axis. Two behaviours peculiar to D1 stimulation included contralateral forepaw myoclonus and forepaw nibbling, which paradoxically was directed mainly ipsilaterally. Each of the behavioural elements occurred independently of the others and after an inexplicably long latency. They were inhibited by the D1 antagonist SCH 23390, but not by the D2 blocking drug metoclopramide. Comparable circling responses were evoked by a D2 agonist (lisuride) injected into the neostriatum after a short delay, and instantaneously by apomorphine (D1/D2 agonist). Both drug behaviours originated diffusely from all parts of the denervated striatum with no obvious "hot-spots", except for circling which exhibited a bimodal distribution rostro-caudally. The actions of lisuride were blocked by systemic metoclopramide, but not by SCH 23390, while the actions of apomorphine were inhibited by both antagonists. Topographies of D2 receptor-mediated events were quite different from those encountered for D1 receptor stimulation by SKF 38393, though neither corresponded to the autoradiographic distribution of D1 and D2 binding sites in the intact striatum. These results reiterate the importance of D1 receptors in motor control and provide a basis for future investigations of the output pathways subserving D1-mediated behaviours.