Estrous cyclicity and the locomotor response to acute and repeated cocaine administration.

Several studies have shown that gonadal hormones modulate the behavioral response to cocaine. In this study we examined if endogenous changes in sex steroids throughout the estrous cycle affect the locomotor response to repeated cocaine administration. Adult female Sprague Dawley rats were cycled for 21 days. Rats then received a daily injection of saline or cocaine (15 mg/kg,i.p.) for 5 days, followed by 7 drug free days. A challenge injection of saline or cocaine (15 mg/kg,i.p.) was given on day 13. Behavioral activity was recorded on days 1, 5 and 13. Vaginal lavages were performed daily, and on days 1, 5 and 13, after behavioral testing. Cocaine increased horizontal activity and total distance traveled of drug naive female rats independent of the stage of the estrous cycle. A similar pattern was observed on day 5 of cocaine treatment. However, after 1 week of withdrawal, rats that were in estrous showed higher cocaine‐induced hyperactivity compared to females in proestrous or diestrous. If we compare cocaine‐induced hyperactivity of females at different stages of the estrous cycle we observe that only females in estrous show an increase from day 1 to day 13, indicating that females in estrous become sensitized to cocaine. These results are similar to those obtained by other groups. An unexpected finding was the shortening of the estrous cycle. In summary, we observed that the stage of the estrous cycle affects the locomotor response to repeated cocaine administration. These data may have implications in treatment strategies for female cocaine addicts.