Cocaine self-administration in ovariectomized rats is predicted by response to novelty, attenuated by 17-beta estradiol, and associated with abnormal vaginal cytology

Parameters of cocaine self-administration behavior and vaginal cytological changes were assessed in ovariectomized rats during and after chronic self-administration. Response to novelty as measured by locomotor activity was found to correlate with cocaine self-administration on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Chronic 17-beta estradiol (E-2) replacement did not affect cocaine self-administration on FR or PR schedules of reinforcement. Acute E-2 administration decreased cocaine self-administration on a PR schedule of reinforcement on the day of and on the two days following hormone treatment. Finally, the proliferation of vaginal epithelia following acute E-2 was potentiated in rats both during cocaine self-administration and 30 days into withdrawal when compared with non-drug-exposed animals. These results identify response to novelty as a behavioral index predictive of cocaine self-administration liability in female rats and additionally provide evidence of psychostimulant-hormonal interactions highly relevant to female behavior and physiology. (C) 1997 Elsevier Science Inc.