Independent mediation of unconditioned motor behavior by striatal D-1 and D-2 receptors in rats depleted of dopamine as neonates

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission yet the specific contribution of D-1 and D-2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intra-striatal injections (0.5 mu l) of DA receptor antagonists' to induce motoric deficits was determined in adult-rats treated with vehicle or 6-OHDA (100 mu g, intraventricular) on postnatal day 3. Administration of the D-1-like antagonist SCH 23390 (0.5-2.0 mu g) or the D-2-like antagonist clebopride (1.0-4.0 mu g) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390+clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D-1 + D-2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D-1- and D-2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D-1 or D-2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.