كاهش وابستگي فيزيكي به مرفين توسط فيتاسترايد (مهاركننده آنزيم 5 آلفا- ردوكتاز) در موش صحرايي نر

Effect of finastride, an inhibitor of 5 alpha-reductase, on physical dependence induced by chronic administration of morphine in male rats

Tolerance and dependence are two main problems which have limited morphine administration as an analgesic drug. Following acute and chronic administration of morphine changes in the level of sex steroids and the activity of calcium channels are reported. The enzyme 5 alpha-reductase plays a pivotal role in the conversion of testostcrone to dehydrotestosterone and therefore reduces the testosterone levels. in this investigation, we tried to study the effects of acute and chronic administration of finastride (inhibitor of 5 alpha-reductase) on morphine dependence in the male rats. Morphine dependency was induced by the intraperitoneal (i.p.) injection of morphine for 4 days (20, 30, 40 and 40 mg/kg respectively at days 1-4). Physical dependence to morphine was observed following administration of naloxone (2 mg/kg-hp., day 5). Acute administration of finastride at 5th day (5 mglkg-i.p., twice with 2 hours interval), decreased al9 withdrawal signs significantly, while the administration the vehicle, caster oil, did not. Chronic administration of finastride prior to daily administration of morphine during days 1-4 significantly decreased all withdrawal signs at the day 5. This finding indicates that inhibition of testosterone metabolism in the CNS using finastride may be able to modulate the withdrawal sings expression and prevents the development of physical dependence.