Comparison of the D1-dopamine agonists SKF-38393 and A-68930 in neonatal 6-hydroxydopamine-lesioned rats: behavioral effects and induction of c-fos-like immunoreactivity.

Administration of the selective D1-dopamine receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393) to neonatal 6-hydroxydopamine-lesioned rats results in profound behavioral manifestations and induction of striatal c-fos-like immunoreactivity. The full D1-dopamine agonist I,[R,S]1-aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran hydrochloride (A-68930), like SKF-38393, produced a dose-dependent, D1-selective increase in locomotor activity and striatal c-fos-like immunoreactivity. These responses were antagonized by a D1-dopamine antagonist, but not by a D2-dopamine antagonist. A-68930 produced locomotor activation at a lower dose than SKF-38393, but no dose of A-68930 was able to produce the magnitude of locomotor activation seen with SKF-38393. Both A-68930 and SKF-38393 induced similar stereotyped behaviors and possessed similar propensities to induce self-injurious behavior in neonatally lesioned rats; however, A-68930 was significantly more potent than SKF-38393 in inducing these behaviors. When either SKF-38393 or A-68930 were administered repeatedly at 2-week intervals, behavioral sensitization (priming) occurred. However, unlike SKF-38393, a high dose of A-68930 produced seizure activity and markedly desensitized D1-dopamine receptor activation for up to 3 days after administration. These results with A-68930 provide additional evidence that the specific behavioral and biochemical responses observed in neonatally lesioned rats after SKF-38393 administration are due to actions on D1-dopamine receptors, and indicate that A-68930 provides a new tool for investigating D1-dopamine receptor function.