Grasshoff_2003_Toxicology_184_149

The severity of poisoning after intoxication with the acetylcholinesterase (AChE) inhibitor soman has been shown to be positively correlated with GABA release in rat striatum. Since most of the neurons in striatum and striatal projection regions use GABA as transmitter, it is still unclear, whether an increase of extracellular GABA in this region results from enhanced activation of these projections or is due to the local effect of AChE inhibition. In this study, the modulation of depolarization-induced increase in GABA concentration by soman was determined in the superfusate of rat striatal slices. Soman and neostigmine increased GABA concentration in the superfusate dose dependently. This increase was exerted through M-cholinoceptors as it could be blocked by atropine and enhanced by application of the muscarinic agonists pilocarpine or oxotremorine. These results clearly indicate that AChE inhibition by soman in rat striatum can directly lead to enhanced release of GABA through M-cholinoceptors.