The potential for progesterone to protect against cocaine-primed relapse in females

Studies in both humans and preclinical animal models suggest that females are more vulnerable to drug addiction than males. Ovariectomy indicates that ovarian hormones may play a key role in predisposing females to addictive tendencies. Isolating the effects of each ovarian hormone (estrogen and progesterone), it appears that estrogen is overall more likely to increase drug-seeking behaviors. Progesterone, however, has been shown to negate the effects of estrogen in the context of cocaine-primed reinstatement of self-administration, a task intended to model relapse. Not only does progesterone\u27s influence on cocaine-seeking behavior complicate the notion that ovarian hormones predispose women to addiction, but it also demonstrates potential for treatment. The present proposal will evaluate whether ovarian hormones underlie females\u27 predisposition to cocaine-primed relapse as well as the extent to which progesterone\u27s attenuation of reinstatement is dependent on high levels of estrogen, specifically with respect to the mesolimbic dopaminergic pathway