The alteration of the GABAergic system in dimethoate intoxication was explored. A rat brain AChE (acetylcholinesterase) activity and GABAergic profiles, including the level of gamma-aminobutyric acid (GABA) and the densities and affinities of gamma-aminobutyric acid A (GABA A ) receptors in the hippocampus, were examined 2 hr after dimethoate administration (0, 38.9, 83.7 and 180.0 mg/kg bw po). The AChE activity was reduced by 60-70% by all three doses of dimethoate. Statistically significant elevation of GABA levels was observed following the administration of dimethoate 180.0 mg/kg bw (121.5% of control, p < 0.05), while the B max values for the GABA A receptors of the hippocampal synaptic membranes were 50.6% and 51.6% of control values in the 83.7 and 180.0 mg/kg bw dimethoate groups, respectively (p < 0.05). Statistically significant decreases in the K d values of 19.8, 51.7, and 53.4% vs. controls were observed in a dose-dependent manner (p < 0.05). In conclusion, it is suggested that the GABAergic system is maybe involved in the neurotoxicity of organophosphates as well as the cholinergic mechanisms.

The effects of acute and subchronic administration of dimethoate on γ-aminobutyric (GABA) concentration and receptor characteristics in rat cerebral cortices were investigated. After a single (acute exposure) or repeated administration of dimethoate, rat cerebral cortex was found to inhibit acetylcholinesterase (AChE) activity in a dosedependent manner. No significant alteration in the concentration of GABA or the numbers of GABA A receptor was noted in cortices of rats after acute exposure to dimethoate except the affinities of the receptor was found elevated significantly following the acute administration. But the GABA concentrations were significantly reduced in the 10 and 20 mg/kg groups after the subchronic dimethoate administration. No difference was found statistically in the GABA A receptor binding in cortices after the subchronic administration of dimethoate. But the K d values were significant decreased reflecting an elevated affinity of receptors in the three dimethoate groups as compared with that of control follow subchronic administration. It is suggested that the GABAergic system is involved in the intoxication of the dimethoate intoxication which is probably to counteract the enhanced cholinergic activity induced by dimethoate.