Involvement of GABA_A receptors in myoclonus

Abstract

Alterations in multiple neurochemical systems have been reported in animal and human studies of posthypoxic myoclonus. It is impossible, however, to establish causative relationships between the observed changes and the myoclonic movements from these studies. Therefore, to establish causative links between neurochemical changes and myoclonus, ligands that target neurotransmitter systems that are altered in posthypoxic myoclonus were microinjected into the lateral ventricles of normal rats to identify the changes that can produce myoclonus. Of the ligands that were tested, only the GABAA antagonists produced myoclonus after intracerebroventricular administration, suggesting the importance of disinhibition of GABAergic systems in myoclonus. To further examine the role of GABA in myoclonus, GABAergic antagonists were microinjected into the nucleus reticularis of the thalamus (NRT), an area of the brain in which extensive pathologic changes are seen in posthypoxic animals. GABAA, but not GABAB, antagonists produced myoclonus after microinjection into the NRT. Earlier investigators have further reported the ability of GABAA antagonists to produce myoclonus after microinjection into the caudate. The data therefore suggest that disruption of activity at GABAA receptors at any one of a number of levels in the neural axis can produce myoclonus.

Lance-Adams Syndrome

“…The loss of serotonin within the inferior olive nucleus has been thought to play a certain role6 and GABA may interact with the serotonin system to suppress posthypoxic myoclonus 7. The treatment of LAS has not been established and a combination of medications based on the neurotransmitters has been reported.…”

Lance-adams syndrome: a report of two cases

“…It is postulated that estrogen, through its regulation of serotonergic activity, may influence the clinical course of PHM (Kompoliti et al, 2001). Other neurotransmitter systems, such as gamma-aminobutyric acid (GABA), may also be involved and interact with the 5-HT system to suppress PHM (Jaw et al, 1996;Matsumoto et al, 2000). Clonazepam was found to have dramatic effects on PHM.…”

Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report

“…The mechanism underlying this movement disorder remains largely unknown. Alterations in multiple neurochemical systems have been reported in animal and human studies, pointing out that abnormalities within the serotonin system and/or a loss of GABA-ergic inhibition may influence the pathophysiological mechanism of PAM 8,9 . According to recent neuroimaging data, it is likely that subcortical neuronal networks including the ventrolateral thalamus are involved 10,11 .…”