Chorea and Myoclonus in the Monkey Induced by Gamma-Aminobutyric Acid Antagonism in the Lentiform Complex

Abstract

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.

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

“…The therapeutic efficacy of naloxone may be caused by the blockade of an increased transmission of endogenous opiates during dyskinesia. Similar to the effects of endomorphin-1, previous studies have shown that the local administration of the GABA receptor antagonist bicuculline in the globus pallidus stimulates dyskinesia (Crossman et al, 1988;Matsumura et al, 1995). In contrast, both local administration of the GABA agonist muscimol in the globus pallidus and chronic peripheral treatment with the opioid antagonist naloxone induced catalepsy in rats (Matsui and Kamioka, 1978;Egan et al, 1995).…”

Spatial and Temporal Properties of Tic-Related Neuronal Activity in the Cortico-Basal Ganglia Loop

“…Specifically, structural and functional imaging studies have found abnormalities in the striatum (Singer and Minzer, 2003), which is the main input structure of the basal ganglia (BG). The direct involvement of the striatum in tics is further supported by findings that disruption of striatal information transmission by localized application of a GABA A antagonist induces motor tics (Tarsy et al, 1978;Crossman et al, 1988;McCairn et al, 2009;Worbe et al, 2009).…”

Disinhibition of the superior colliculus restores orienting to visual stimuli in the hemianopic field of the cat

“…In the present study, it was assumed that the mechanism by which the GABA A antagonist leads to recovery is one of disinhibition. Although there is no direct physiological evidence in this study to confirm that SC cells were disinhibited (i.e., depolarized), other studies using similar volumes and concentrations of bicuculline methiodide have demonstrated depolarization and have reported similar immediate postinjection effects (Chevalier et al, 1981;Hikosaka and Wurtz, 1985a;Buee et al, 1986;Crossman et al, 1988;Yoshida et al, 1991;Dean and Redgrave, 1992;Matsumura et al, 1995).…”