Involvement of the GABAergic System in Dimethoate-induced Intoxication

Abstract

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 (GABAA )r eceptors in the hippocampus, were examined 2h r 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 followin gt he administration of dimethoate 180.0 mg/kg bw (121.5% of control, p < 0.05), while the Bmax values for the GABAA 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 Kd 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.