An animal model of compulsive sexual behavior induced by morphine

Abstract

It is well recognized that psychoactive drugs impact sexual function, performance, and arousal. Chronic use of drugs in general leads to compulsive sexual behavior (CSB) in substance abusers and causes high rates of sexually transmitted diseases, including HIV, although different drugs are associated with variable degrees of sexual risk behavior. Existing research has consistently demonstrated high rates of cooccurrence between CSBs and substance use disorders, with comorbidity rates ranging from 40% to 60%. Morphine is one of the most abusive illicit drugs in the world. Similar to effects of psychostimulants, morphine abuse is commonly associated with loss of sexual inhibition and subsequent compulsive sexual behavior, including heightened sexual desire, numerous sexual partners, and lack of protection. Previous research has focused almost exclusively on the effects of drugs of abuse on sexual motivation and performance. Although such effects are indeed reported in humans as well, the human studies have indicated that one of the largest and most problematic effects of drugs on sex behavior is the increase in risk-taking behaviors related to sexual activity. Yet, few animal studies have attempted to investigate this phenomenon, in part probably due to a lack of an established paradigm to study CSB in rodents. This study aims to develop an animal model of CSB in morphine pretreated (total 330 mg/kg; i.p. 5 d) male rats by a sexual aversion conditioning paradigm, in which increasing intensity foot-shock is paired with sexual contact to assess the compultive motivation. Following 7 d morphine withdrawal, a sexually receptive female rat is placed in the stimuluscage, the male rat can contact with the female rat by going through an electric rods. The current value of the electric rods was increased after each trial according to the following: 0.2, 0.3, 0.4, 0.6, 0.8, 1, 1.4, 1.8 mA. To avoid foot damage, the cut-off of 2 mA was introduced. The results show that morphine pretreated group expresses a persistent preference toward the sexually receptive female despite the foot-shock, as indicated by a significant increase in the current value compared to saline pretreated group. Moreover, the compulsive motivation to approach a sexually receptive female rat is no difference betweent saline pretreated rats and morphine pretreated but sexually naive rats, thereby suggesting that sexual experience in male rats is a critical influence factor for CSB. We think the model has a higher face and predictive validity compared to previous models and the model will help further examine the neurobiological underpinnings of CSB as well as providing a tool to study the influence factors on CSB in detail.