Effect of Testosterone on the Extinction Period of Morphine-induced CPP in Male Rats

Background: Sex-related differences in the incidence, prevalence, symptoms, and side effects of drug use, especially narcotics, have been previously shown in animal models and human studies. Objectives: In the presents study, the effects of different doses of testosterone on morphine extinction period were investigated in a rat model. Methods: Forty mature male Wistar rats were randomly allocated to four categories (10 in each group), including control (received intramuscular injection of vehicle) and testosterone (received intramuscular injection of testosterone at 1, 2.5 and 5 mg/kg) during the extinction period. Conditioned place preference (CPP) test was done to assess the psychological phenomena of drug craving and relapse. The CPP score was calculated in five stages, including the baseline (preconditioning), acquisition (conditioning), expression (postconditioning), extinction, and reinstatement. Results: Our results demonstrated that testosterone (1, 2.5 and 5 mg/kg) significantly extended morphine extinction duration compared to the control group. It has been shown that dopamine neurotransmission in mesocorticolimbic system is affected by testosterone through androgen receptors in adolescence and alteration in testosterone level could affect drug use vulnerability. Conclutions: It seems that normalization of testosterone levels reduces the symptoms of opioid withdrawal syndrome and have important clinical implication for clinicians to understand the effects of testosterone dysregulation on the extinction and withdrawal periods.