Abstract
The selective M 4 muscarinic receptor toxin, MT3, was used in vivo to evaluate the role of M 4 receptors in cholinergic inhibition of neuropeptide mRNA expression in striatonigral neurons. Unilateral injection of the muscarinic toxin 3 (0.04–4 nmol) into the dorsal striatum of chronically-cannulated rats elevated basal levels of preprodynorphin, substance P and preproenkephalin mRNAs in the ipsilateral dorsal striatum as revealed by quantitative in situ hybridization. Pretreatment with muscarinic toxin 3 also augmented amphetamine (2.5 mg/kg, i.p.)-stimulated preprodynorphin and substance P expression in the dorsal striatum in a manner similar to that observed after the muscarinic antagonist, scopolamine. Since muscarinic toxin 3 has a much greater affinity for muscarinic M 4 receptors than for other subtypes, it is possible that muscarinic toxin 3, by interacting with the muscarinic M 4 subtype, regulates basal and/or dopamine-stimulated striatal neuropeptide gene expression.
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