The effect of paraoxon on GABA uptake in rat cerebellar synaptosomes

The compounds used to treat organophosphate (OP) poisoning are not able to fully alleviate long-lasting effects. They are mainly used to antagonize the cholinergic effects of OPs; however, non-cholinergic effects such as interference with different neurotransmitter systems, especially GABA release and uptake, are now attracting more attention.

Cerebellar synaptosomes were used to investigate any potential interaction between paraoxon and GABA uptake. The cerebella of 250- to 280-g Wistar rats were rapidly dissected out, homogenized, centrifuged, and incubated with 0.004 microM [(3)H]GABA in the presence of different doses of paraoxon for 15 minutes at 37 degrees C. At the end of the incubation period, the synaptosomes were layered in chambers of a superfusion system (UGO). To assay the amount of [(3)H]GABA uptake, radioactivity was measured using a beta-counter (Winspectrul).

Mean GABA uptake was 111, 95, 71, 73, and 75 percent of the control values in the presence of paraoxon concentrations of 0.01, 0.1, 1, 10, and 100 microM, respectively. Accordingly, GABA uptake was significantly reduced at doses 1, 10, and 100 microM of paraoxon (P<0.05).

Paraoxon may interfere with GABA uptake by cerebellar synaptosomes at micromolar concentrations or higher.