Impaired ontogeny of striatal dopamine D1 and D2 binding sites after postnatal treatment of rats with SCH-23390 and spiroperidol.

The effect of chronic postnatal treatment of rats with selective D1- and/or D2-receptor antagonists on the development of D1- and D2-receptors in the striatum was studied. When neonatal rats were treated postnatally from the day of birth for 32 successive days with the D1-receptor antagonist, SCH-23390 (0.30 mg/kg i.p.), the development of striatal dopamine D1-receptors was markedly impaired, and the development of striatal D2-receptors was slightly impaired. Alternatively, chronic treatment with the D2-receptor antagonist, spiroperidol (1.0 mg/kg i.p.), resulted in a markedly impaired development of striatal dopamine D2-receptors, and a slightly impaired development of striatal D1-receptors. Scatchard analysis revealed that chronic SCH-23390 treatment during development resulted in a 78% decrease in the Bmax for in vitro binding of [3H]SCH-23390 to striatal homogenates, while the Kd was unaltered. Similarly, chronic postnatal treatment with spiroperidol was associated with a 74% reduction in the Bmax, while the Kd for in vitro binding of [3H]spiroperidol to striatal homogenates was unchanged. These findings demonstrate that chronic selective dopamine receptor antagonism affects development of both striatal D1- and D2-receptor types. The critical period during which striatal dopamine receptor ontogeny can be altered is not restricted to prenatal periods, since suitable postnatal challenge will alter striatal dopamine-receptor development.