Co-activation of D1- and D2-like receptors is unnecessary for stimulated motor behavior in rats depleted of dopamine during development

Abstract

The motoric effects of the D1-like agonist SKF 38393 (5.0 or 20.0 mg/kg) and the D2-like agonist quinpirole (0.2, 1.0, or 3.0 mg/kg) were determined in adult rats treated with 6-OHDA (100 μg) or its vehicle on postnatal Day 3. Quinpirole, but not SKF 38393, produced stereotypy and modest motor activity in vehicle-treated rats. These effects of quinpirole were blocked by either the D1-like antagonist SCH 23390 (0.2 or 0.4 mg/kg) or the D2-like antagonist clebopride (10.0 mg/kg). In contrast, administration of either D1- or D2-like agonists enhanced stereotypy and motor behavior in animals depleted of dopamine with 6-OHDA. However, in these animals, only the D1-like antagonist was able to block D1-induced behaviors and only the D2-like antagonist was able to block D2-induced behaviors. A separate group of adult rats, treated with 6-OHDA (200 μg) on postnatal Day 20, was studied to determine whether these effects depended upon age at the time of DA depletion. Animals depleted on Day 20 resembled animals depleted on Day 3 in that D2-, but not D1-like antagonists, blocked D2 agonist-induced responses. These results demonstrate that in animals depleted of DA during development, qualitative changes in D1/D2 receptor interactions result in the ability of each receptor subtype to independently activate stereotypy and motor behavior.