Involvement of GABA(A) receptors in myoclonus

Alterations in multiple neurochemical systems have been reported in animal and human studies of posthypoxic myoclonus. It is impossible, however, to e stablish causative relationships between the observed changes and the myocl onic movements from these studies. Therefore, to establish causative links between neurochemical changes and myoclonus, ligands that target neurotrans mitter systems that are altered in posthypoxic myoclonus were microinjected into the lateral ventricles of normal rats to identify the changes that ca n produce myoclonus. Of the ligands that were tested, only the GABA(A) anta gonists produced myoclonus after intracerebroventricular administration, su ggesting the importance of disinhibition of GABAergic systems in myoclonus. To further examine the role of GABA in myoclonus, GABAergic antagonists we re microinjected into the nucleus reticularis of the thalamus (NRT), an are a of the brain in which extensive pathologic changes are seen in posthypoxi c animals. GABA(A), but not GABA(B), antagonists produced myoclonus after m icroinjection into the NRT. Earlier investigators have further reported the ability of GABA(A) antagonists to produce myoclonus after microinjection i nto the caudate. The data therefore suggest that disruption of activity at GABA(A) receptors at any one of a number of levels in the neural axis can p roduce myoclonus.