Use of ³H-muscimol for GABA receptor studies

Abstract

γ-AMINOBUTYRIC ACID (GABA) is a major transmitter in the mammalian central nervous system (CNS)^1,2 and studies of synaptic receptors for neurotransmitters have been useful in many areas of neuropharmacology^3,4. Although GABA receptors can be studied using ³H-GABA itself^5–7, a ligand which does not bind to GABA uptake sites would be valuable for autoradiography and for other studies of receptor function. Muscimol (3-hydroxy-5-aminomethyl-isoxazole) is a naturally occurring GABA analogue found in Amanita muscaria^8,9. It is reported to be a potent agonist at bicuculline-sensitive, strychnine-insensitive postsynaptic receptors of the mammalian CNS^10–12 and to have minimal affinity for the GABA uptake system¹³. Muscimol also seems to enter the brain after peripheral injection¹⁴ and is aldehyde fixable. I here present evidence of the binding of ³H-muscimol by brain tissue, comparing binding by membrane preparations in vitro with retention of ³H-muscimol after intravenous administration. The ability of muscimol to alter evoked release of GABA by synaptosomes was also used to verify the ability of muscimol to alter the function of GABA neurones.