g-Amino-butyric acid (GABA) is the major inhibitory transmitter in the CNS, and has many effects that are opposite to those of glutamate, some of which involve GABAergic inhibition of glutamate function. The GABA uptake inhibitor, CI-966 9, has been associated with psychotic episodes in humans,17 a similar phenotype to that seen with the psychotomimetics that block the effects of glutamate at the NMDA receptor. A role of GABA in the etiology of schizophrenia was first proposed in the early 1970s based on GABAergic regulation of DA neuronal function with a special focus on the role of GABA in working memory. GABA uptake sites are decreased in hippocampus, amygdala, and left temporal cortex in schizophrenics with some evidence of GABAa receptor upregulation18 and reductions in GABA interneurons.19 An extensive review of the use of benzodiazepines, the classical GABAA agonists, the GABAg agonist baclofen 10, and the anticonvulsant valproic acid (VPA; 11), the latter being used as a potential GABAergic agent, in combination with antipsychotics in clinical studies noted mixed results.18
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