Brain Research, 424 (1987) 37-48 37 Elsevier BRE 12966 Substantia nigra and motor control in the rat: effect of intranigral a-kainate and 7-D-glutamylaminomethylsulphonate on motility Lechoslaw Turski, Thomas Klockgether*, Waldemar Turski**, Michael Schwarz*** and Karl-Heinz Sontag Max-Planck-lnstitutefor Experimental Medicine, GOttingen (F.R.G.) (Accepted 24 March 1987) Key words: a-Kainic acid; y-D-Glutamylaminomethylsulphonic acid; Substantia nigra; Caudate-putamen; Muscle tone; Catalepsy; Turning; Electromyogram; 6-Hydroxydopamine; Ibotenic acid Bilateral microinjections of an excitatory amino acid, a-kainate (KA), 5-50 ng, into the substantia nigra pars reticulata (SNR) re- sult in an increase in the muscle tone and catalepsy in rats. The preferential KA/quisqualate antagonist, y-D-glutamylaminomethyl- sulphonate (y-D-GAMS), 10 #g, blocks the actions of KA, 25 ng, when coadministered into the SNR. The chemical lesion of the cau- date-putamen with 6-hydroxydopamine (6-OHDA) does not affect either increases in the muscle tone or catalepsy produced by KA, 25 ng, from the SNR. The lesion of the caudate-putamen with ibotenate moderately enhances the effect of KA, 25 ng, on the muscle tone. Microinjections of KA, 25 ng, into the substantia nigra pars compacta (SNC) do not increase the muscle tone and lead to signifi- cantly less pronounced catalepsy relative to that observed following the injections of KA into the SNR. Unilateral microinjections of KA, 10-50 ng, into the SNR elicit ipsilateral turning in rats in a dose- and time-dependent manner, Unilateral application of ~,-D- GAMS, 1-10gg, into the SNR produces contralateral turning. The turning evoked by KA, 25 ng, or y-D-GAMS, 10#g, is affected neither by 6-OHDA nor by ibotenate lesion of the caudate-putamen. These results demonstrate that excitatory neurotransmission in the substantia nigra participates in the regulation of the muscle tone and posture in rats. INTRODUCTION Excitatory amino acids, L-glutamate or L-aspar- tate, subserve neurotransmitter function in the corti- conigral pathway 3't3'24. A high density network of glutamate-immunoreactive nerve terminals was demonstrated to be present in the pars compacta (SNC) and to a lesser extent in the pars reticulata (SNR) of the substantia nigra 24. The substantia nigra constitutes a target of conver- gence of different inputs arising from the basal gan- glia, limbic forebrain and cortex 2'27. This brain area relays and transforms motor and sensory information setting gains and biases over the spinal motor cen- ters 4'27'4°. L-Glutamate is regarded as a putative neurotransmitter which contributes to the complex function of the substantia nigra in the motor con- trol 1'25,26. Three types of receptors for excitatory amino acids, N-methyl-D-aspartate (NMDA), a-kai- nate (KA) and quisqualate (QA), may be activated by L-glutamate in the mammalian CNS 12'42. Mona- ghan et al. 2°-23 first demonstrated receptor binding of KA, RS-a-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA) and 2-amino-7-phosphono- heptanoic acid (AP7) to neuronal membranes in the rat substantia nigra. Selective antagonism at nigral glutamate-sensitive NMDA-receptors with AP7 re- sults in anticonvulsant and myorelaxant effect in ro- dents 8,31,41. The delineation of the physiological role of non-NMDA receptors is hindered by the lack of * Present address: Department of Neurology, Eberhard-Karls-University, Liebermeisterstr. 18-20, D-7400 Tfibingen, F.R.G. ** Present address: Maryland Psychiatric Research Center, P.O. Box 3235, Baltimore, MD 21228, U.S.A. *** Present address: Department of Neurology, Alfried Krupp Hospital, Alfried-Krupp-Str. 21, D-4300 Essen, F.R.G. Correspondence: L. Turski. Present address: Department of Neuropsychopharmacology, Schering AG, Sellerstr. 6-8, Postfach 65 03 11, D-1000 Berlin 65, F.R.G. 0006-8993/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)