Effect of Paraoxon on GABA Uptake by Rat Cerebral Cortex Synaptosomes

Background: It has been suggested that organophosphates may inhibit gamma-aminobutyric acid (GABA) metabolism in synaptosomal preparations. In the present investigation, we have assessed the interaction between paraoxon and the GABA system at synaptic level. Methods: Synaptosomes were prepared from male Wistar rats (200-250 g). Cerebral cortex was dissected and homogenized, then centrifuged at 1000g for 5 min and again at 12000g for 20 min. The pellet containing synaptosomes was resuspended in the buffer solution and the protein concentration adjusted at 1 mg/ml. Determination of lactate dehydrogenase (LDH) activity, as a biochemical index for synaptosomal integrity, was assessed. Cholinesterase activity of synaptosomes was also determined. Synaptosomes were preincubated for 20 min with two concentrations of paraoxon (10-9-10-3M), and then incubated with [3H]GABA for 10 min, before being washed through 0.65 μm filters. Results: Paraoxon inhibited cholinesterase activity of synaptosomes in a concentration dependent manner. Synaptosomal accumulation of [3H] GABA/GABA was time dependent and peaked at 15 min. Paraoxon significantly increased the uptake in nano molar concentrations and decreased it at higher concentrations. Conclusion: The result of this study indicate that in synaptosomes prepared from rat cerebral cortex paraoxon increases GABA uptake at low dose and inhibits its uptake at high doses. This may imply a role for organophosphate-induced convulsion, which needs further clarification.Iran J Med Sci 2006; 31(3):125-130. Keywords ● Synaptosome ● GABA ● organophosphate ● paraoxon