INTERACTIONS BETWEEN D1 AND MUSCARINIC RECEPTORS IN THE INDUCTION OF STRIATAL C-FOS IN RATS DEPLETED OF DOPAMINE AS NEONATES

The contributions of striatal DI receptors to the expression of sensor imotor behavior are qualitatively different in rats depleted of dopami ne (DA) as neonates vs. as adults. In an effort to reveal neuronal mec hanisms underlying these behavioral differences we determined the effe cts of the partial D1 agonist SKF 38393, the muscarinic antagonist sco polamine, and the combination of the two drugs on the induction of c-f os in the striatum and its projection sites, the globus pallidus and s ubstantia nigra. Adult rats, given intracerebroventricular injections of 6-hydroxydopamine (6-OHDA, 50 mu g/5 mu l/hemisphere) or its vehicl e on postnatal day 3, were treated with SKF 38393 (1.5 mg/kg, i.p.), s copolamine (5.0 mg/kg, i.p.) or the combination of the two drugs. Ther e was no significant induction of c-fos in vehicle-treated controls, r egardless of drug administration. In DA-depleted rats, scopolamine als o did not induce c-fos whereas SKF 38393 produced a significant increa se in the number of FOS-positive cells in the dorsal, but not ventral, striatum. The combined administration of scopolamine and SKF 38393 re sulted in a potent synergism in tile number of FOS-positive cells in D A-depleted rats. These interactions between lesion condition and drugs on c-fos induction were not secondary to differences in drug-induced behavioral activity. Activity levels were no different in vehicle vs, DA-depleted rats following the combined administration of scopolamine + SKF 38393, yet the two groups of rats exhibited marked differences i n the density of FOS-positive striatal neurons. The effects of scopola mine and SKF 38393 on c-fos induction in striatum are qualitatively si milar to those reported in rats DA-depleted as adults and suggest that , at this single-label level of analysis, the ability of D1 and muscar inic receptors to influence striatal activity does not contribute to t he marked age-related differences in the behavioral effects of DA depl etions.