Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra.

Two unilateral injections of 6-hydroxydopamine into the substantia nigra and ventral tegmental area of adult rats pretreated with desmethylimipramine produced severe unilateral depletions of limbic and striatal dopamine. These animals sustained global deficits in spontaneous motor activity with no recovery evident from 1 to 14 weeks postoperative. The frequency of spontaneous circling increased during the 1st few weeks postoperative and then remained stable during the last 2 months of observation. The changes in circling were independent of changes in global spontaneous motor behaviors. Biochemical determinations indicated an increased dopamine turnover in residual limbic and striatal dopamine neurons but with substantially changed dihydroxyphenylacetic acid:homovanillic acid ratios. The absence of functional recovery of both normal and asymmetric motoric behavior indicates that severe uncompensated deficits in motoric function produced by unilateral 6-hydroxydopamine lesions can provide a useful animal model for the study of dopaminergic contributions to movement disorders.