The inhibitory effect of Paraoxon on cerebellar synaptosome GABA uptake in rats

Introduction: Compounds which are used to treat organophosphate (OP) poisoning are not able to fully alleviate long lasting effects. They are mainly used to antagonize cholinergic effects of Ops. However, non-cholinergic effects, such as interference with different neurotransmitter systems, especially GABA release and uptake, are recently attracting more attentions. We have tried to investigate any potential interaction between paraoxon and GABA uptake. Methods: We used cerebellar synaptosomes. Cerebellum of 250-280 g Wistar rats were rapidly dissected out, homogenized, centrifuged, and incubated with 0.01 μ M [3H]GABA in the presence of different doses of paraoxon for 10 minutes at 37 oC. At the end of the incubation period, synaptosomes were layered in chambers of superfusion system. In order to assay the amounts of [3H]GABA taken up, radioactivity was measured using a β-counter. Results: Our findings reveal that mean GABA uptake was 111.42, 95.37, 71.6, 73.53 and 75 percent of the control values in the presence of different concentrations of paraoxon (0.01, 0.1, 1, 10 and 100μ M) respectively. GABA uptake was significantly reduced at doses 1, 10 and 100μ M (p<0.05). Conclusion: It seems that paraoxon at higher doses may interfere with GABA uptake by cerebellar synaptosomes.