Chorea and myoclonus in the monkey induced by gamma-aminobutyric acid antagonism in the lentiform complex. The site of drug action and a hypothesis for the neural mechanisms of chorea.
Experiments are described in which the gamma-aminobutyric acid (GABA) antagonist bicuculline was injected into the lentiform complex of conscious monkeys. Injections into either the lateral segment of the globus pallidus, or the medial part of the putamen, gave rise to chorea of the contralateral limbs and/or orofacial region. Control injections of vehicle alone were without effect. Injections of bicuculline into the lateral part of the putamen gave rise to contralateral myoclonus. The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus. It is proposed that the primary site of action of the GABA antagonist in producing chorea, in the present studies, was the lateral segment of the globus pallidus. The mode of action is suggested to be interruption of GABAergic transmission from the striatum to the lateral pallidal segment. Since this also occurs in Huntington's disease, it is proposed that experimental chorea induced by this method in the monkey may be a useful model of the dyskinesia seen in Huntington's disease in man. Loss of influence of inhibitory striatopallidal fibres would lead to abnormally increased activity of lateral pallidal neurons. These in turn project to the subthalamic nucleus, upon which they have an inhibitory action. Dyskinesia is thus produced by physiological inhibition of the subthalamic nucleus, whose destruction, both in man and the monkey, is known to produce ballism. It is proposed that ballism and chorea share common neural mechanisms, both involving the loss of influence of the subthalamic nucleus on the medial segment of the globus pallidus.
Crossman
A R
AR
Department of Cell and Structural Biology, School of Biological Sciences, University of Manchester.
Mitchell
I J
IJ
Sambrook
M A
MA
Jackson
A
A
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D002819:Chorea / Q000503:physiopathology*; D003342:Corpus Striatum / Q000378:metabolism*; D018756:GABA Antagonists; D008252:Macaca fascicularis; D008254:Macaca nemestrina; D008959:Models, Neurological; D009068:Movement; D009207:Myoclonus / Q000139:chemically induced* / Q000503:physiopathology; D010215:Papio
D018756:GABA Antagonists; D001640:Bicuculline