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 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 GABA(A) 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. GABA(A), but not GABA(B), antagonists produced myoclonus after microinjection into the NRT. Earlier investigators have further reported the ability of GABA(A) antagonists to produce myoclonus after microinjection into 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 produce myoclonus.
Matsumoto
R R
RR
University of California Irvine, Department of Neorology, California, USA.
Truong
D D
DD
Nguyen
K D
KD
Dang
A T
AT
Hoang
T T
TT
Vo
P Q
PQ
Sandroni
P
P
D000818:Animals; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology; D004831:Epilepsies, Myoclonic / Q000503:physiopathology*; D006801:Humans; D002534:Hypoxia, Brain / Q000503:physiopathology*; D020646:Intralaminar Thalamic Nuclei / Q000503:physiopathology; D009207:Myoclonus / Q000503:physiopathology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*
D011963:Receptors, GABA-A