Bhargava H N, Zhao G M
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Health Sciences Center, 60612, USA.
Neuropeptides. 1996 Jun;30(3):219-23. doi: 10.1016/s0143-4179(96)90067-0.
The effects of NG-nitro-L-arginine (NNA), an inhibitor of nitric oxide synthase (NOS) on the development of tolerance to the analgesic action of D-Pen2, D-Pen5 enkephalin (DPDPE), a delta 1 opioid receptor agonist, and morphine were determined in the mouse. Tolerance to DPDPE was induced in male Swiss-Webster mice by twice daily intracerebroventricular (i.c.v.) injections of the drug (20 micrograms/mouse) for 4 days. NNA was injected intraperitoneally (i.p.) 10 min before each injection of DPDPE. Chronic injections of DPDPE resulted in development of tolerance to its analgesic action. Multiple injections of NNA by itself did not modify the analgesic response to DPDPE. Concurrent injections of NNA did not affect the development of tolerance to the analgesic action of DPDPE. Twice daily injections of morphine (15 mg/kg s.c.) for 4 days resulted in the tolerance to its analgesic action. Concurrent administration of NNA with morphine attenuated the development of tolerance to morphine. It is concluded that NOS inhibition attenuates morphine, but not delta, opioid agonist-induced tolerance in the mouse.
在小鼠中测定了一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸（NNA）对δ1阿片受体激动剂D-青霉胺2，D-青霉胺5脑啡肽（DPDPE）和吗啡镇痛作用耐受性发展的影响。通过每天两次脑室内（i.c.v.）注射该药物（20微克/小鼠），持续4天，诱导雄性瑞士-韦伯斯特小鼠对DPDPE产生耐受性。在每次注射DPDPE前10分钟腹腔内（i.p.）注射NNA。慢性注射DPDPE导致对其镇痛作用产生耐受性。多次单独注射NNA并未改变对DPDPE的镇痛反应。同时注射NNA并不影响对DPDPE镇痛作用耐受性的发展。每天两次皮下注射吗啡（15毫克/千克），持续4天，导致对其镇痛作用产生耐受性。NNA与吗啡同时给药减弱了对吗啡耐受性的发展。得出的结论是，在小鼠中，抑制NOS可减弱吗啡诱导的耐受性，但不能减弱δ阿片受体激动剂诱导的耐受性。
