Majeed N H, Przewłocka B, Machelska H, Przewłocki R
Neuropeptide Research Department, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Neuropharmacology. 1994 Feb;33(2):189-92. doi: 10.1016/0028-3908(94)90006-x.
The effect of the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 5-20 mg/kg i.p.) and NG-nitro-L-arginine (NO2Arg, 5-20 mg/kg i.p.) on morphine-induced analgesia, as well as on morphine induced tolerance and dependence was examined in male albino Swiss mice. Neither acute nor repeated (for 5 days) administration of the nitric oxide synthase inhibitor, L-NAME affected the morphine induced analgesia, as measured by hot plate and tail-flick tests. On the other hand, administration of L-NAME or NO2Arg along with morphine prevented the development of tolerance to the analgesic effect of morphine for at least 7 days, whereas the analgesic effect of morphine alone disappeared after 5 days. L-NAME and NO2Arg also attenuated some signs of morphine dependence, as assessed by naloxone (2 mg/kg)-precipitated withdrawal. These results indicate that NO may play a role in the development of morphine tolerance and dependence.
在雄性白化瑞士小鼠中，研究了一氧化氮（NO）合酶抑制剂L-NG-硝基精氨酸甲酯（L-NAME，腹腔注射5-20mg/kg）和NG-硝基-L-精氨酸（NO2Arg，腹腔注射5-20mg/kg）对吗啡诱导的镇痛作用以及吗啡诱导的耐受性和依赖性的影响。通过热板法和甩尾试验测量，一氧化氮合酶抑制剂L-NAME无论是急性给药还是重复给药（连续5天），均不影响吗啡诱导的镇痛作用。另一方面，L-NAME或NO2Arg与吗啡联合给药可至少7天预防对吗啡镇痛作用的耐受性形成，而单独使用吗啡的镇痛作用在5天后消失。通过纳洛酮（2mg/kg）诱发的戒断反应评估，L-NAME和NO2Arg也减轻了吗啡依赖性的一些体征。这些结果表明，NO可能在吗啡耐受性和依赖性的形成中起作用。
