Unilateral 6-hydroxydopamine lesions of dopamine neurons produce bilateral self-stimulation deficits

Sixteen rats, which had electrode implants in each hemisphere which generated comparable self-stimulation rate-intensity functions, were used in this study. Eight of the rats received unilateral 6-hydroxydopamine injections into the substantia nigra pars compacta, which produced severe unilateral losses of dopamine and were effective in generating apomorphine-induced turning away from the injected hemisphere. Of the remaining 8 rats, 5 received unilateral 6-hydroxydopamine lesions aimed at the ventral tegmental area and 3 were give vehicle injections. The vehicle injections were without effect on self-stimulation and the ventral tegmental injections had an overall transient facilitative effect on self-stimulation. The 6-hydroxydopamine lesions of the pars compacta, however, had variable effects. In some rats there was a marked bilateral reduction in self-stimulation over 8 weeks; whereas, there was little, if any, effect in other rats. The rats which sustained the bilateral deficits also sustained the greatest unilateral loss of dopamine. The unilateral 6-hydroxydopamine lesions of the pars compacta consistently blocked the facilitative influence of 0.5 mg/kg of D-amphetamine on self-stimulation bilaterally, and this effect persisted over 8 weeks of postoperative testing. These results were considered supportive of a response rather than reinforcement role for dopamine in the mediation of self-stimulation behavior.