THE MUSCARINIC TOXIN-3 AUGMENTS NEUROPEPTIDE MESSENGER-RNA IN RAT STRIATUM IN-VIVO

The selective M-4 muscarinic receptor toxin, MT3, was used in vivo to evaluate the role of M-4 receptors in cholinergic inhibition of neurop eptide mRNA expression in striatonigral neurons. Unilateral injection of the muscarinic toxin 3 (0.04-4 nmol) into the dorsal striatum of ch ronically-cannulated rats elevated basal levels of preprodynorphin, su bstance P and preproenkephalin mRNAs in the ipsilateral dorsal striatu m as revealed by quantitative in situ hybridization. Pretreatment with muscarinic toxin 3 also augmented amphetamine (2.5 mg/kg, i.p.)-stimu lated preprodynorphin and substance P expression in the dorsal striatu m in a manner similar to that observed after the muscarinic antagonist , scopolamine. Since muscarinic toxin 3 has a much greater affinity fo r muscarinic M, receptors than for other subtypes, it is possible that muscarinic toxin 3, by interacting with the muscarinic M:, subtype, r egulates basal and/or dopamine-stimulated striatal neuropeptide gene e xpression. (C) 1997 Elsevier Science B.V.