Effect of testosterone on morphine withdrawal syndrome in rats

Aim： To determine whether testosterone is involved in morphine withdrawal syndrome （WS）. Methods： In order to induce dependency, rats were treated with subcutaneous injection of morphine （days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg）, and after the last dose of morphine （day 8） WS was induced by intraperitoneal injection of naloxone （1 mg/kg）. Wet dog shake （WDS）, abdomen writhing （AW）, and jumps （J） were recorded as indicators of WS. Results： The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated （10 mg/kg/day for 8 days, i.p.） male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy （10 mg/kg/day for 8 days, i.m.） in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats. Conclusion： It can be concluded that testosterone might be effectively involved in morphine WS.