Sex differences in vulnerability to drug self-administration.

Recent evidence from both human and animal studies indicates that there are sex differences in all phases of the addiction process, including initiation and acquisition of use, patterns and levels of use, the progression to addiction, and relapse. This brief review summarizes a series of studies on sex differences in drug self-administration in rats on which the Wyeth Young Psychopharmacologist Award was based and relates these findings to human clinical data. Briefly, preclinical findings show that female rats acquire drug self-administration at a faster rate, work harder to obtain drug infusions, "binge" for longer initial periods of time and show a more diurnally dysregulated pattern of self-administration under extended-access conditions, and respond at higher levels under reinstatement testing conditions compared with male rats. Similar results have been reported in humans, suggesting a biological basis of sex differences in vulnerability to drug abuse. A number of biological mechanisms have been explored, and the results show that ovarian hormones play a critical role in modulating the reinforcing effects of drugs of abuse in females. Preclinical studies, in conjunction with human studies, should further inform a sex-specific model for differences in drug abuse, and such a model may be useful for developing prevention and treatment strategies for drug abuse.