The effect of nitric oxide synthesis inhibition on intravenous cocaine self-administration.

Adult male rats were implanted with intravenous catheters. After a minimum of 10 days recovery from surgery, rats were trained to intravenously self-administer cocaine (1 mg/kg/infusion) during 3-h test sessions. The nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) was used to determine the effect of nitric oxide (NO) synthesis inhibition on cocaine self-administration. A 5-day protocol was used and on Days 2 and 5, an intraperitoneal injection of L-NAME (0, 3, 30, 300 mg/kg) was administered 45 to 60 min into a 3-h test session. One to two hours following L-NAME administration, there was a dose-dependent decrease in the amount of self-administered cocaine and an increase in the interresponse time (IRT) between successive cocaine injections. L-NAME appeared to prolong the rewarding effect of cocaine possibly through a pharmacokinetic action.