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COMPARISON OF THE D1-DOPAMINE AGONIST SKF-38393 AND A-68930 IN NEONATAL 6-OHDA-LESIONED RATS: BEHAVIORAL EFFECTS AND INDUCTION OF C-FOS-LIKE IMMUNOREACTIVITY
Citation:
Johnson, K., H. Criswell, K. Jensen, P. Simpson, R. Mueller, AND G. Breese. COMPARISON OF THE D1-DOPAMINE AGONIST SKF-38393 AND A-68930 IN NEONATAL 6-OHDA-LESIONED RATS: BEHAVIORAL EFFECTS AND INDUCTION OF C-FOS-LIKE IMMUNOREACTIVITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/375 (NTIS PB93107209), 1992.
Description:
Previous studies from this laboratory and others have found that neonatal 6-OHDA-lesioned rats exhibit profound behavioral manifestations, and significant induction of striatal c-fos-like immunoreactivity (FLI), when administered the selective D1-dopamine agonist SKF-38393. ith the recent report of the full D1-dopamine agonist A-68930, we examined responses of A-68930 on behavior and FLI in neonatally lesioned rats, and compared these responses to those found after administration of SKF-38393. n neonatally lesioned rats, both SKF-38393 and A-68930 produced dose-dependent, D1-selective increases in locomotor activity and striatal FLI. owever, A-68930 was unable to produce the magnitude of locomotor activation seen with SKF-38393, and higher doses of the D1-dopamine antagonist SCH-23390 were needed to block the activity and FLI induced by A-68930 than by SKF-38393. oth A-68930 and SKF-38393 induced similar stereotyped behaviors, and possessed similar propensities to induce self-injurious behavior in neonatally lesioned rats. hen either SKF-38393 or A-68930 were administered repeatedly at two week intervals, behavioral sensitization (priming) occurred. owever, unlike SKF-38393, a large dose of A-68930 markedly desensitized D1-dopamine receptor activation for up to 3 days after administration and produced seizure activity. hese results with A-68930 provide additional evidence that the specific behavioral and biochemical responses observed in neonatally lesioned rats.
