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J.Health Sci., 53(5), 527-533, 2007
Involvement of the GABAergic System in Dimethoate-induced Intoxication
Qiang En Wu, Ting Ting Ban,
Xiu Li Chang, Tai Yi Jin,
You Xin Liang, Qing Wu,
and Zhi Jun Zhou*
Department of Occupational Health and Toxicology, Fudan University School of Public Health, 138 Yixueyuan Road, Shanghai 200032, China and Key Laboratory of Public Health and Safety (Ministry of Education), 138 Yixueyuan Road, Shanghai 200032, China
The alteration of the GABAergic system in dimethoate intoxication was explored. A rat brain AChE (acetyl-cholinesterase) activity and GABAergic profiles, including the level of gamma-aminobutyric acid (GABA) and the densities and affinities of gamma-aminobutyric acid A (GABAA) 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 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.
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