Imaging the Role of GABA in Movement Disorders

Abstract

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. This paper reviews the current knowledge derived from positron emission tomography and single photon emission tomography studies quantifying GABAA receptor binding in movement disorders of extrapyramidal origin, focusing on essential tremor (ET), Parkinsonism (idiopathic PD and atypical parkinsonian syndromes), dystonia, and Huntington's disease (HD). In ET, there is evidence to suggest a specific disturbance at the level of the GABAA receptor and impairment of GABAergic inhibition to be a driving force for the development of rhythmic overactivity in cerebello-thalamo-cortical networks. In dystonia, GABAA receptor binding studies have been relevant for unraveling pathophysiological mechanisms causing sensorimotor disinhibition leading to dystonic movements. The role of GABA in idiopathic PD and atypical parkinsonian syndromes is less clear, despite the fact that GABAA receptors are expressed on virtually all striatal neurons and that GABA exerts important inhibitory influences upon basal outflow pathways. In HD, reductions of GABAA receptor have been reported in the basal ganglia but were found to be less extensive compared with concomitant metabolic reductions.