Objective: The role of nitric oxide (NO) in excitotoxicity of kainic acid (KA) in the brain was investigated.
Methods: Adult female rats were bilaterally intra-caudate nucleus injected with KA. The nitric oxide synthase (NOS) was determined by measuring NO2- concentration produced from homogenized brain tissue in the enzyme response system at three time point after surgery. Another groups of rats were daily administrated (i.p.) L-NAME(10 mg/kg) or 7-NI(25 mg/kg) at 2nd to 6th day after intra-caudate KA injection. Behavioral tests for learning and memory were started at 10th day after surgery.
Results: NOS activity in caudate nucleus remained unchanged in 6-8 hours after surgery. It increased significantly in 3 days and slightly increased in 5 days after surgery. Both L-NAME and 7-NI ameliorated memory impairment induced by KA injection in passive avoidance response task. Only L-NAME improved KA-induced deficit in active avoidance response behavior.
Conclusions: This study gives further evidence that NOS activation and excessive NO may mediate KA-induced excitotoxicity. Early and repetitive use of NOS inhibitors shows some protective effect on memory deficit induced by KA excitotoxicity.