Muscarinic receptors regulate striatal neuropeptide gene expression in normal and amphetamine-treated rats

This study investigated the effects of pharmacological blockade or stimulation of muscarinic receptors on constitutive and amphetamine-stimulated preprodynorphin, substance P and preproenkephalin gene expression in rat striatum. Acute administration of the non-selective muscarinic antagonist, scopolamine (2.5, 5 and 10 mg/kg, s.c.), caused a dose-dependent increase in preprodynorphin and substance P, but not preproenkephalin, messenger RNA expression in the dorsal and ventral striatum as revealed by quantitative in situ hybridization. In contrast, acute injection of the nonselective muscarinic receptor agonist, oxotremorine (0.125, 0.25 and 0.5 mg/kg, s.c.), caused a dose-dependent increase in basal levels of preproenkephalin messenger RNA in the dorsal striatum, without causing a significant effect on constitutive striatal preprodynorphin and substance P expression. Pretreatment with scopolamine (2.5 mg/kg, s.c.) significantly augmented striatal induction of preprodynorphin and substance P messenger RNA induced by acute injection of amphetamine (1.25 and 2.5 mg/kg, i.p.), whereas scopolamine blocked amphetamine-stimulated striatal preproenkephalin expression. Pretreatment with oxotremorine (0.25 mg/kg, s.c.) significantly attenuated amphetamine (1.25 and 2.5 mg/kg, i.p.)-stimulated striatal preprodynorphin and, to a lesser degree, substance P messenger RNA expression. Oxotremorine tended to increase amphetamine-stimulated preproenkephalin messenger RNA expression, but the effect did not reach statistical significance. Ln addition, scopolamine increased spontaneous, and enhanced amphetamine-stimulated; behavioral activity, whereas oxotremorine attenuated amphetamine-stimulated behaviors. These data support the concept that cholinergic transmission, via interaction with muscarinic receptors, inhibits basal and D-1 receptor-stimulated striatonigral dynorphin/substance P gene expression and facilitates striatopallidal enkephalin gene expression. Copyright (C) 1996 IBRO.