Involvement of the GABAergic System in Dimethoate-induced Intoxication

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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 2hr after dimethoate administration (0, 38.9, 83.7 and 180.0mg/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 180.0mg/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 180.0mg/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.
社団法人日本薬学会の論文
2007-10-01