Estrous cycle influence on individual differences in the response to novelty and cocaine in female rats

In rats, individual differences in vulnerability to self-administration of drugs of abuse can be predicted by individual locomotor responses to a novel environment. This phenomenon has been well described for male rats, however very little information is available with regard to female rats and the added complication of estrous cycle hormone changes influencing activity levels. This study was designed to explore the relationship between individual responsiveness to exposure to a novel environment, the estrous cycle, and the response to cocaine in intact, cycling female rats. Locomotor activity of naive female rats was measured upon exposure to a novel environment followed by determination of estrous cycle stage and level of circulating estradiol. Rats were identified as high-responder (HR; 15% most active) or low-responder (LR; 15% least active) rats based on the locomotor response. Hyperactivity in response to cocaine was greater in HR than in LR rats. These data in combination with evaluation of the stage of estrous suggest that the estrous cycle interacts with individual phenotypic characteristics to modify the sensitivity to cocaine in female animals.