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.