Differential effects of pallidal lesions on the behavioural responses to SKF 38393, LY 171555 and apomorphine in the rat

Abstract The purpose of this study was to determine the role of the globus pallidus in the expression of dopamine D 1 - and D 2 -receptor mediated motor events. Rats were first injected stereotaxically with 6-hydroxydopamine in one medial forebrain bundle to denervate the ascending dopamine pathways in that hemisphere. Apomorphine and selective D 1 and D 2 agonists were then administered, at two dose levels, to establish characteristic response patterns. Subsequently the animals were given a secondary lesion by injecting kainic acid (0.2–1 μg) into the ipsilateral globus pallidus and retested with the dopamine agonists over a period of two months. The kainate treatment itself caused spontaneous motor asymmetries, followed by aphagia, adipsia and hypersensitivity to touch. Contraversive circling, contralateral posture and grooming induced by systemic apomorphine were all abolished by the kainate treatment, whilst sniffing and head movements were facilitated. All activities induced by D 1 stimulation were abolished or severely reduced under these conditions. By contrast, the contralateral posture and grooming elicited by D 2 stimulation were spared, and only D 2 -dependent contraversive rotation, sniffing and head movements were reduced. All behavioural deficits were temporary and recovered partially or completely during the course of the experiment, but could not be overcome by increasing the dose of dopamine agonist. Post mortem histology revealed a consistent loss of pallidal neurons, together with more variable damage to extrapyramidal structures and the thalamus. The results show that all the D 1 -mediated, and certain of the D 2 -mediated motor responses depend on the integrity of the pallidum for their expression in the unilaterally 6-hydroxydopamine-treated rat.