The Pharmacology of 3H-Muscimon Binding of GABA Post-Synaptic Receptors: An Attemtp to Determine GABA's Role in Schizophrenia
Wheeler, Robert Leonard, III
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Gamma-aminobutyric acid (GABA) is now a well accepted inhibitory neurotransmitter in the vertebrate central nervous system. Through radioassays using [3H]-muscimol as a ligand, the pharmacology of Na+-independent GABA post-synaptic receptors was determined. This was done on three different brain tissues: the whole brain minus the cerebellum, the cortex, and the cerebellum. It was found that binding at the GABA receptor was specific and saturable satisfying two criterion for a neurotransmitter receptor. Scatchard and Hill Plot analysis of the regional areas showed that the cortex contained the highest density (Bmax) of GABA receptors followed by the cerebellum. The cerebellum was shown to have a significantly (P=O.003) greater affinity (KD) for GABA then receptors in the cortex. This result could possibly prove the existence of two distinct GABA receptor sites in the mammalian brain. Acute and chronic studies were also done using chlorpromazine, an antipsychotic drug, in order to evaluate the GABA hypothesis of schizophrenia. The hypothesis suggests a hypofunction of GABA activity upon dopamine neurons. The results from this study showed that GABA has very little, if anything, to do with schizophrenia symptoms.