Brain Research, 373 (1986) 365-372 365 Elsevier BRE 11703 The Role of Striatal Cholinergic Mechanisms for the Development of Limb Rigidity: An Electromyographic Study in Rats MICHAEL SCHWARZ, CHRYSANTHY IKONOMIDOU, THOMAS KLOCKGETHER, LECHOSLAW TURSKI*, BART ELLENBROEK** and KARL-HEINZ SONTAG Max-Planck-lnstitutefor Experimental Medicine, D-3400 G6ttingen (F.R.G.) (Accepted October 2rid, 1985) Key words: bethanechol-- electromyography-- muscimol-- muscular rigidity-- neostriatum-- N-methylscopolamine - - substantia nigra The muscarinic cholinergic agonist bethanechol (0.25-1.0 gg) injected bilaterally into various parts of the rat neostriatum induced a tonic electromyogram (EMG) activity in the gastrocnemius muscle which is considered to be a measure of limb rigidity. This tonic EMG activity was found to be dose-dependent and muscarine-specific since it could be blocked by coadministration of the muscarinic antagonist N-methylscopolamine (1.0/zg). Tonic EMG activity of comparable amount was observed after injections of bethanechol (1.0/~g) into all regions of the neostriatum but not into the giobus pallidus, thalamus, zona incerta or cortex. The tonic EMG activity induced by intrastriatal injection of bethanechol (1.0/~g) was abolished by a subsequent injection of the GABAmimetic drug muscimol (25 rig) into the posterior part of the substantia nigra pars reticulata suggesting that bethanechol-induced limb rigidity is mediated via impairment of GABAergic transmission within the substantia nigra pars reticulata. INTRODUCTION The neostriatum is among those brain regions con- taining high amounts of the neurotransmitter acetyl- choline, its synthesizing enzyme choline acetyltrans- ferase, its degrading enzyme acetylcholinesterase and muscarinic receptors (for references see ref. 14). Lesion studies suggest that the cholinergic markers are due to the presence of cholinergic neurons intrin- sic to the striatuml,20. Although the presumed striatal cholinergic interneurons represent only a small frac- tion of the whole striatal cell population they provide a dense cholinergic innervation within the neostria- tum (for references see ref. 11). The involvement of central cholinergic mecha- nisms in the regulation of muscle tone is strongly sug- gested by the observation that anticholinergic drugs exert a beneficial effect on Parkinsonian rigidity2. Moreover, systemic administration of the muscarinic cholinergic agonist tremorine is capable of inducing muscular rigidity in experimental animalslO,2S. The finding that a bilateral kainic acid lesion of the neo- striatum prevents the tremorine-induced rigidity un- derlines the importance of the neostriatum for the ex- pression of the latter effectZS. There is increasing evidence from neurochemical and neuroanatomical studies that the neostriatum represents an inhom0geneous structure receiving and giving rise to topographically organized pathways (for references see ref. 14). Behavioral studies give further support to the hypothesis of striatal inhomo- geneity. Intrastriatal injection of drugs that influence dopaminergic, GABAergic and cholinergic transmis- sion have been found to result in different behavioral responses in relation to the site of application of each drug3,7,9,21,25,30. * On leave from: Department of Pharmacology, Institute of Clinical Pathology, Medical School, Jaczewskiego 8, PL-20-090 Lublin, Poland. ** Present address: Psychoneuropharmacoiogical Research Unit, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Correspondence: M. Schwarz, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, D-3400, G6ttingen, F.R.G.