Synaptosomal GABA uptake decreases in paraoxon-treated rat brain

Abstract

A synaptosomal model was used to evaluate in vivo effects of paraoxon on the uptake of [(3)H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats were given a single intraperitoneal injection of one of three doses of paraoxon (0.1, 0.3, or 0.7 mg/kg) and acetylcholinesterase (AChE) activity in the plasma, cerebral cortex, and hippocampus was measured at 30 min, 4h, and 18 h after exposure. [(3)H]GABA uptake in synaptosomes was also studied in another series of animals. Paraoxon administration (0.3 and 0.7 mg/kg) caused significant inhibition of AChE activity in the plasma and both brain areas at all time points. 0.1 mg/kg paraoxon significantly inhibited AChE activity but only in the plasma for 4h, the activity was completely recovered at 18 h. GABA uptake was significantly (p<0.001) reduced in both cerebral cortex (18-32%) and hippocampal (16-23%) synaptosomes at all three time points after administering 0.7 mg/kg of paraoxon, a dose that seems to be sufficient to induce seizure activity. L-DABA, an inhibitor of neuronal GABA transporter, allowed us to conclude that the uptake was mediated primarily by neuronal GABA transporter GAT-1. In conclusion, present data suggests that GABA uptake by synaptosomes decreases probably secondary to paraoxon-induced seizure activity.