D1- and D2-receptor mediation of motoric behavior in rats depleted of DA as neonates: effects of age and size of depletion.

The D1/D2 mediation of motor behavior in rats is qualitatively altered following large forebrain dopamine (DA) depletions on postnatal day 3. These animals are markedly subsensitive, relative to controls or animals depleted of DA as adults, to the motoric deficits produced by individual D1- or D2-like antagonists but are impaired following combined D1 +D2 antagonists. In order to determine the extent of DA depletion necessary to produce this subsensitivity to individual antagonists, we compared the motoric effects of D1 and D2 antagonists in adult animals sustaining a wide range of DA depletions on day 3. Only animals with striatal depletions of > or = 95% demonstrated this subsensitivity to individual antagonists. Moreover, since important changes in DA receptor ontogeny occur during the first postnatal week, we compared the ability of the D1-like antagonist, SCH 23390 (0.2 mg/kg), or the D2-like antagonists, clebopride (10.0 mg/kg) and haloperidol (1.0 mg/kg), to induce akinesia or catalepsy in adults depleted of DA on either day 1 or on day 3. Rats depleted of striatal DA (> 95%) at either age exhibited similar subsensitivity to D1 or D2 antagonists. These findings suggest that large DA depletions are necessary to alter the roles of D1 and D2 receptors in the expression of motor behavior and that this plasticity is comparable in animals depleted on day 1 or day 3.