The proposed study investigates the influence of estrous cycling upon cocaine abuse behavior in female rats. It is designed to examine the relationship between the estrous cycle and dopamine receptor influence upon reinforcement mechanisms. Cocaine self-administrative on fixed and progressive ratio schedules will serve as reinforcement models with response levels compared to estrous cycle timing. Rat estrous cycles will be monitored daily through histological analysis of vaginal smears and will be correlated to cocaine self-administration responses. The relative roles of dopamine D1, D2 and D3 receptors in female rats reinforcement mechanisms will be compared to those of males through evaluation of animal responses to selective dopamine agonists/antagonists. In females, selectiv dopamine agonists/antagonists will be substituted for cocaine at select points within the estrous cycle. Responses at estrus will be compared to those two days post-estrus for each drug tested. Study results will serve to define the relative influence of the various dopamine receptor subtypes in female reinforcement mechanisms as well as to provide insight into any fundamental distinctions between male and female reinforcement mechanisms.
