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 (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.

Effects of Acute and Subchronic Exposures to Dimethoate on Rat Cerebral Cortex GABAergic System

“…Then the GABA and internal standard were separated with a HP-1100 HPLC system and be detected at a fluorescence detector (Hewlett-Packard, Boeblingen, Germany) using isocratic elution as previously described. 23) A Hypersil octadecyl silica (ODS)-3 column (4.6 × 250 mm, 5 µm, GL, Kyoto, Japan) was used in the HPLC system. The mobile phase was potassium dihydrogen phosphate buffer (0.1 mol/l, pH 6.0) containing 30% methanol and 10% acetonitrile delivered at a flow rate of 1.0 ml/min which was filtered through a 0.2 µm nylon membrane and degassed by ultrasonification before use.…”