Sahraei Hedayat, Poorheidari Gholamreza, Foadaddini Mohsen, Khoshbaten Ali, Asgari Alireza, Noroozzadeh Ali, Ghoshooni Hassan, Firoozabadi Seyed Hassan, Zarrindast Mohammad Reza
Department of Physiology, Baghyatallah (a.s.) University of Medical Sciences, Tehran, Iran.
Pharmacol Biochem Behav. 2004 Jan;77(1):111-6. doi: 10.1016/j.pbb.2003.10.008.
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.
先前的研究报道，吗啡部分通过释放一氧化氮（NO）发挥其作用。在本研究中，研究了急性和慢性给予NO前体L-精氨酸和NO合酶（NOS）抑制剂L-硝基-氨基-甲酯（L-NAME）对大鼠吗啡自我给药的影响。动物最初被训练使用食物作为强化物按压杠杆。通过外科手术给大鼠植入一根慢性硅橡胶导管，导管置于颈外静脉。手术后5天，训练它们按压杠杆进行药物自我给药。目前的数据表明，L-精氨酸（0.05、0.1和0.15毫克/千克/注射）而非L-NAME（0.05、0.1和0.15毫克/千克/注射）诱导了自我给药行为并增加了运动。L-精氨酸（0.1毫克/千克/注射）诱导的反应在预先给予L-NAME（5、10和15毫克/千克腹腔注射）后减弱。急性（5、10和15毫克/千克腹腔注射）和慢性（200毫克/千克腹腔注射；每天两次，共4天）给予L-精氨酸均减少了吗啡自我给药。然而，急性（5、10和20毫克/千克腹腔注射）和慢性（50毫克/千克腹腔注射；每天两次，共4天）给予L-NAME显著增加了吗啡自我给药。可以得出结论，NO可能在吗啡自我给药中起作用。
