Lesions of the globus pallidus, entopeduncular nucleus and substantia nigra alter dopamine mediated circling behaviour

Abstract

Unilateral kainic acid lesions of the globus pallidus in the rat caused weak spontaneous circling at 3 and 10 days after surgery. Unilateral kainic acid lesions of the entopeduncular nucleus caused no spontaneous circling at any time after surgery. Systemic administration of apomorphine to such lesioned animals caused ipsiversive circling in both groups. Pallidal lesions in animals with a prior ipsilateral 6-OHDA lesion of the medial forebrain bundle attenuated apomorphine-induced, but not amphetamine-induced, circling. Entopeduncular nucleus lesions in the 6-OHDA lesioned animal attenuated both apomorphine- and (+)-amphetamine-induced circling. Kainic acid lesions of the globus pallidus or entopeduncular nucleus did not alter nigral glutamic acid decarboxylase (GAD) activity. Unilateral electrolytic lesions of the globus pallidus or entopeduncular nucleus caused ipsiversive circling in response to apomorphine. An electrolytic lesion of the globus pallidus in animals with a prior 6-OHDA lesion did not alter (+)-amphetamine-induced circling but reversed the direction of apomorphine-induced circling. Electrolytic lesions of the entopeduncular nucleus enhanced (+)-amphetamine-induced circling and attenuated apomorphine-induced circling. Nigral GAD activity was reduced by electrolytic lesions of the globus pallidus but not by those of the entopeduncular nucleus. Large kainic acid lesions in the area of the substantia nigra caused weak spontaneous contraversive circling 3 days after surgery, and ipsiversive circling in response to the systemic administration of apomorphine. Similar lesions in animals with a prior ipsilateral 6-OHDA lesion of the medial forebrain bundle initially attenuated the response to (+)-amphetamine, but the response returned with time. The direction of apomorphine-induced circling was reversed in these animals. The strio-nigral pathway and nigral efferents are confirmed to be involved in circling induced by dopamine agonists in rats with a unilateral lesion of the medial forebrain bundle. Both the globus pallidus and the entopeduncular nucleus also appear to be involved in this dopamine-mediated circling behaviour.