Roles of catecholamine terminals and intrinsic neurons of the ventral tegmentum in self-stimulation investigated in neonatally dopamine-depleted rats.

Three series of experiments were undertaken to determine whether the residual catecholamine (CA) terminals or intrinsic neurons of ventral tegmentum (VT) in rats given 6-hydroxydopamine (6-OHDA) after desmethylimipramine (DMI) in the lateral ventricles at birth, mediated VT self-stimulation (SS). In Experiment I, male pups were injected bilaterally on days 3 and 5 with 6-OHDA (total dose 200 micrograms) or with the vehicle after pretreatment with DMI (50 mg/kg, IP) 30 min earlier. Each subject, 150 days old, was implanted bilaterally in the VT with electrode-cannula units. Both the dopamine (DA)-depleted and control groups yielded similar percentages of self-stimulators. The rate of responding was, however, slightly but significantly lower in the DA-depleted group than in the controls. In Experiment II, 8 DA-depleted and 7 control rats were pretreated with pargyline (50 mg/kg, IP) and then given unilateral injections of 6-OHDA in the VT, in the tissue below the SS electrode. These intracerebral injections of 6-OHDA had no effect on VT SS in both groups. Seventeen controls and 12 DA-depleted rats, in Experiment III, were given injections of kainic acid (KA; 5 nM) either ipsilaterally or contralaterally. The ipsilateral injection abolished SS (14 days of testing), whereas the contralateral injection had no effects on ipsilateral SS in both groups. Histochemical fluorescence study in Experiment I and II showed that the neonatal treatment with DMI + 6-OHDA had reduced the number of DA-containing perikarya in the VT and that reinjection of 6-OHDA into the VT caused the disappearance of the residual CA terminals in tissue surrounding the electrode tip.