Verdi Javad, Ahmadiani Abolhassan
Department of Physiology and Pharmacology, Kashan University of Medical Sciences, Kashan, Iran.
Horm Behav. 2007 May;51(5):605-10. doi: 10.1016/j.yhbeh.2007.02.008. Epub 2007 Mar 2.
It has been shown that morphine increases 5alpha-reductase enzyme activity in the rat central nervous system; however importance of this finding on morphine analgesia, tolerance and dependence has not been reported. In the present study, we investigated inhibition of 5alpha-reductase enzyme on morphine effects using finasteride. To determine whether the 5alpha-reductase enzyme interact with morphine analgesia, finasteride (5 mg/kg, i.p.) was administrated with morphine (5 and 7 mg/kg, i.p.). The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 45, 60 and 90 min after drug administration. In tolerance experiments, morphine 20 mg/kg was injected i.p., twice daily for 4 days. The development and expression of dependence were assessed in the naloxone precipitation test 5 days after the morphine (20-30 mg/kg, i.p.) administration. We found that finasteride could potentiate the antinociceptive effect of morphine. In addition, chronic finasteride administration effectively blocked development of tolerance and dependence to morphine. Following chronic morphine administration, single dose injection of finasteride failed to reverse tolerance but prevented naloxone precipitate withdrawal syndrome. Therefore, it was concluded that there is a functional relationship between 5alpha-reductase enzyme and morphine.
研究表明，吗啡可增加大鼠中枢神经系统中5α-还原酶的活性；然而，这一发现对吗啡镇痛、耐受性和依赖性的重要性尚未见报道。在本研究中，我们使用非那雄胺研究了5α-还原酶对吗啡作用的抑制情况。为了确定5α-还原酶是否与吗啡镇痛相互作用，将非那雄胺（5毫克/千克，腹腔注射）与吗啡（5和7毫克/千克，腹腔注射）联合给药。在给药前以及给药后15、30、45、60和90分钟，使用甩尾试验评估伤害性感受阈值。在耐受性实验中，腹腔注射20毫克/千克吗啡，每天两次，共4天。在吗啡（20 - 30毫克/千克，腹腔注射）给药5天后，通过纳洛酮催瘾试验评估依赖性的发展和表现。我们发现非那雄胺可增强吗啡的镇痛作用。此外，长期给予非那雄胺可有效阻止对吗啡耐受性和依赖性的发展。长期给予吗啡后，单次注射非那雄胺未能逆转耐受性，但可预防纳洛酮诱发的戒断综合征。因此，得出结论：5α-还原酶与吗啡之间存在功能关系。
