Monoamine release from dopamine-depleted rat caudate nucleus reinnervated by substantia nigra transplants: An in vivo electrochemical study

Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a dopamine (DA)-denervated caudate nucleus can reverse a number of the behavioral abnormalities induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of potassium (K⁺) from DA-depleted, SN transplant-reinnervated striatum. Animals were injected unilaterally with 6-hydroxydopamine (6-OHDA) into the SN and screened by measuring apomorphine-induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. Nafion-coated graphite epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from ascorbate or acidic DA metabolites. The GEC electrode was fixed to a K⁺-filled micropipette and this assembly was used to map the caudate nucleus of control, 6-OHDA-treated, and 6-OHDA-treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate. By contrast, releases from striatal sites further distal from transplants were markedly reduced to about 30% of control; similar values were obtained from 6-OHDA-treated striata which did not received SN grafts. The time course of the K⁺-evoked releases was also reduced following 6-OHDA treatment, but returned to control values in striatal sites proximal to a transplant. The data thus lend further evidence to the postulate that SN grafts ameliorate lesion-induced behavioral dysfunctions by providing specific DA input to the host brain.