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

• Published in: Neuroscience Vol. 75; no. 1; pp. 43 - 56
• Main Authors: Wang, J.Q, McGinty, J.F
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.1996; Elsevier
• Subjects: Acetylcholine - physiology; Amphetamine - pharmacology; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; dynorphin; Dynorphins - biosynthesis; Dynorphins - genetics; enkephalin; Enkephalins - biosynthesis; Enkephalins - genetics; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Male; Medical sciences; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Nerve Tissue Proteins - physiology; Neuropeptides - biosynthesis; Neuropeptides - genetics; Neuropharmacology; nucleus accumbens; oxotremorine; Oxotremorine - pharmacology; Pharmacology. Drug treatments; Protein Precursors - biosynthesis; Protein Precursors - genetics; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptors, Dopamine D1 - physiology; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; scopolamine; Scopolamine - pharmacology; substance P; Substance P - biosynthesis; Substance P - genetics; NAc, nucleus accumbens; PPD, preprodynorphin; enkephalin; dynorphin; oxotremorine; SP, substance P; PPE, preproenkephalin; nucleus accumbens; substance P; scopolamine; Rat; CNS stimulant; Psychotropic; Substance P; Rodentia; Central nervous system; Enkephalin; Basal ganglion; Corpus striatum; Gene expression; Opioid peptide; Neuropeptide; Cholinergic receptor; Vertebrata; Mammalia; Animal; Dynorphin; Muscarinic receptor; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(96)00277-1

This study investigated the effects of pharmacological blockade or stimulation of muscarinic receptors on constitutive and amphetamine-stimulated preprodynorphin, substance P and preproenkephalin gene ppeexpression 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 non-selective 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. In 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.