EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITORS ON COCAINE SENSITIZATION

Behavioral sensitization to cocaine was tested for in rats pretreated with a nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) or 7-nitro indazole (7-NI). A 5-day pre-exposure to once daily cocaine (15 mg/kg, i.p.) injections yielded sensitizati on to cocaine (15 mg/kg)-induced behavioral activation. Pretreatment i njections of L-NAME (100 mg/kg) or 7-NI (30 mg/kg), administered 30 mi n before each cocaine pre-exposure injection, acutely inhibited cocain e-induced behavioral activation. No sensitization was found after L-NA ME pretreatment in a protocol with a 3-day withdrawal between pre-expo sure and test cocaine injections. With a 10-day withdrawal period, coc aine sensitization was prevented by L-NAME or 7-NI pretreatment. These results after a 10-day withdrawal are unlikely to arise from deficien t brain NO synthase activity on the test day. Instead, these findings suggest a role for NO in mechanisms underlying the development of coca ine sensitization. We conclude that NO participates in both the develo pment of sensitization as well as the expression of cocaine-induced be havior in previously drug-naive animals.