DISCRIMINATIVE STIMULUS EFFECTS OF COCAINE IN FEMALE VERSUS MALE-RATS

Eight female and 8 male rats were trained to discriminate 5.6 mg/kg i. p. cocaine from saline on a 2-lever, food-reinforced drug discriminati on procedure. Female rats acquired the cocaine discrimination in appro ximately the same number of sessions that males did(43 +/- 7 vs. 51 +/ - 9 sessions, respectively), and the ED(50) for cocaine discrimination was nearly equivalent in female and male rats(2.46 +/- 0.41 vs. 2.32 +/- 0.49 mg/kg, respectively). The time course for cocaine discriminat ion was similar in female and male rats, except the offset of cocaine' s effects occurred significantly earlier in females than in males. D-A mphetamine dose-dependently substituted for cocaine in all 7 males and 6 of 7 females tested, with no significant sex difference in the ED(5 0) values for D-amphetamine substitution. None of the three opioid ago nists tested, morphine (mu), U69,593 (kappa) or BW373U86 (delta), full y substituted for cocaine in rats of either sex. The dopamine antagoni st fluphenazine blocked the discriminative stimulus effects of cocaine to approximately the same extent in both sexes. Further drug discrimi nation training with a higher dose of cocaine, 10 mg/kg, did not signi ficantly alter the ED(50) for cocaine discrimination, and there was st ill no significant sex difference in ED(50) values (3.50 +/- 0.39 vs. 2.36 +/- 0.41 mg/kg in females vs. males, respectively). In these same rats, however, cocaine (1-10 mg/kg) produced significantly greater lo comotor activation in females than in males on a test of spontaneous l ocomotor activity. Thus, these results suggest that there are few sex differences in discriminative stimulus effects of cocaine, even at dos es that produce significantly different locomotor responses in female versus male rats.