ABSTRACT
Generally speaking, adult men report higher rates of drug use initiation and regular use compared to women. However, epidemiological trends indicate that women progress more rapidly from initiation of use to entry into treatment. Moreover, a growing body of evidence suggests that compared to men, women experience higher levels of craving and relapse during periods of abstinence. Neuroendocrine mechanisms are responsible for mediating some of these sex differences. Studies have demonstrated that a woman’s response to the subjective effects of drugs of abuse varies with her menstrual cycle. Sex differences in drug reward and reinforcement are mediated, in part, through the effects of gonadal hormones on mesolimbic reward systems and anti-reward/stress pathways in the brain. Here, we will review basic neurocircuitry that underlies reward and addiction, highlighting neuroadaptive changes that occur in the mesolimbic reward and anti-reward/stress pathways. We propose that sex differences are due to hormonal influences on the neural substrates that mediate positive and negative reinforcement; and that this differential influence, which serves to uniquely guide motivational behaviors, may underlie the factors that cause women to be more vulnerable to develop and sustain an addiction than men.
