Effects of nitric oxide on morphine self-administration in rat

Previous studies have reported that morphine exerts its effects in part through the release of nitric oxide (NO). In the present study, the effects of acute and chronic administration of the NO precursor, L-arginine and NO synthase (NOS) inhibitor, L-nitro-amino-methyl-ester (L-NAME) on morphine self-administration in rats were investigated. The animals were initially trained to press a lever using food as reinforcer. Rats were surgically prepared with a chronic Silastic catheter implanted in the external jugular vein. Five days after surgery, they were trained to press a lever for drug self-administration. The present data indicate that L-arginine (0.05, 0.1, and 0.15 mg/kg/injection) but not L-NAME (0.05, 0.1, and 0.15 mg/kg/injection) induced self-administration behavior and increased locomotion. The response induced by L-arginine (0.1 mg/kg/injection) was reduced by pretreatment with L-NAME (5, 10, and 15 mg/kg ip). Both the acute (5, 10, and 15 mg/kg ip) and the chronic (200 mg/kg ip; twice daily for 4 days) administration of L-arginine reduced morphine self-administration. However, acute (5, 10, and 20 mg/kg ip) and chronic (50 mg/kg ip; twice daily for 4 days) administration of L-NAME increased morphine self-administration significantly. It can be concluded that NO may have a role in morphine self-administration.