Supersensitivity to dopamine agonists following unilateral, 6-hydroxydopamine-induced striatal lesions in mice

Abstract

Following an injection of 6-hydroxydopamine into the left striatum, mice initially circled spontaneously in the direction of the lesion and gradually developed an ability to circle in the opposite direction when challenged with apomorphine or L-dopa. Dose-response curves for apomorphine- and L-dopa-induced circling rates shifted to the left as the duration between the time of the 6-hydroxydopamine injection and the time of testing increased from 2 to 30 days. There was a positive correlation between the rate of apomorphine-induced circling and the reduction in the dopamine concentration in the lesioned forebrain. Doses of apomorphine and L-dopa required to elicit circling responses were 1/6 to 1/10 of those required to increase locomotor activity in normal mice. These data support the concept of development of supersensitivity of postsynaptic dopaminergic receptors in the lesioned striatum.