Restoration of dopamine overflow and clearance from the 6-hydroxydopamine lesioned rat striatum reinnervated by fetal mesencephalic grafts.

The purpose of these experiments was to investigate the electrochemical indices of mesencephalic dopaminergic grafts as they function in the rat striatum. Sprague-Dawley rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle, and the effectiveness of these lesions was tested by measuring apomorphine-induced rotation. The unilaterally lesioned rats were later transplanted with fetal ventral mesencephalon. Only animals receiving ventral mesencephalon transplants showed significant decreases in rotation after grafting. High-speed chronoamperometric recording techniques using Nation-coated carbon fiber electrodes were used to evaluate dopamine (DA) overflow in the striatum of urethane-anesthetized rats. We found that 6-hydroxydopamine lesions resulted in a loss of KCl-induced DA overflow and clearance. Ventral mesencephalon grafts restored neurochemical indices. The zone of normalized DA clearance was considerably larger than that of normalized release. Furthermore, histochemical studies using tyrosine hydroxylase immunoreactivity confirmed graft survival and neurite outgrowth from the graft into the lesioned striatum. In conclusion, these findings suggest that the behavioral improvements by grafts of fetal mesencephalic tissue are accompanied by morphological and electrochemical evidence of reinnervation and the restoration of DA input. Measurement of DA clearance may reveal a wider area of reinnervation than that indicated by more traditional immunocytochemical methods.