Effect of Paraoxon on GABA Uptake by Rat Cerebral Cortex Synaptosomes

Background: it has been suggested that organophosphatesmay inhibit gamma-aminobutyric acid (gaba) metabolism insynaptosomal preparations. in the present investigation, wehave assessed the interaction between paraoxon and thegaba system at synaptic level.methods: synaptosomes were prepared from male wistar rats(200-250 g). cerebral cortex was dissected and homogenized,then centrifuged at jooog for 5 min and again at 12000g for20 min. the pellet containing synaptosomes was resuspendedin the buffer solution and the protein concentration adjusted ati mg/ml. determination of lactate dehydrogenase (ldh) activity,as a biochemical index for synaptosomal integrity, wasassessed. cholinesterase activity of synaptosomes was alsodetermined. synaptosomes were preincubated for 20 min withtwo concentrations of paraoxon (10. 9-1 0·3 m), and then incubatedwith [3h]gaba for 10 min, before being washedthrough 0.65 urn filters.results: paraoxon inhibited cholinesterase activity ofsynaptosomesin a concentration dependent manner. synaptosomalaccumulation of [3h] gaba/gaba was time dependent andpeaked at 15 min. paraoxon significantly increased the uptakein nano molar concentrations and decreased it at higherconcentrations.conclusion: the result of this study indicate that in synaptosomesprepared from rat cerebral cortex paraoxon increasesgaba uptake at low dose and inhibits its uptake at high doses.this may imply a role for organophosphate-induced convulsion,which needs further clarification.