Sex differences in the neurobiology of drug addiction

Epidemiological data demonstrate that while women report lower rates of drug use than men, the number of current drug users and abusers who are women continues to increase. In addition women progress through the phases of addiction differently than men; women transition from casual drug use to addiction faster, are more reactive to stimuli that trigger relapse, and have higher rates of relapse then men. Sex differences in physiological and psychological responses to drugs of abuse are well documented and it is well established that estrogen effects on dopamine (DA) systems are largely responsible for these sex differences. However, the downstream mechanisms that result from interactions between estrogen and the effects of drugs of abuse on the DA system are just beginning to be explored. Here we review the basic neurocircuitry which underlies reward and addiction; highlighting the neuroadaptive changes that occur in the mesolimbic dopamine reward and anti-reward/stress pathways. We propose that sex differences in addiction are due to sex differences in the neural systems which mediate positive and negative reinforcement and that these differences are modulated by ovarian hormones. This forms a neurobehavioral basis for the search for the molecular and cellular underpinnings that uniquely guide motivational behaviors and make women more vulnerable to developing and sustaining addiction than men.