Figure 1. Effect of estradiol benzoate (EB) on the motivation to obtain cocaine.

Ovariectomized (OVX) female rats were prepared for self-administration as previously described [62]. Rats were trained on an FR1 and then an FR2 schedule of reinforcement while receiving 0.4 mg/kg/infusion cocaine, and then were transferred to a progressive ratio (PR) schedule as described by Roberts [104]. Animals were assigned to one of 2 groups: 1) OVX treated with oil 30 min prior to the PR test session for 5 days then no treatment for 2 days (OVX+OIL, N=9); or 2) OVX rats treated with 5 μg EB 30 min prior to the PR session for the first 5 days, and then no treatment for 2 days (OVX+EB, N=12). The Mean +/− SEM number of responses per 4 h progressive ratio test session is illustrated. During the first week the cocaine dose received was 0.3 mg/kg/infusion, during the second week 0.4 mg/kg/infusion, and during the last week 0.5 mg/kg/infusion. Analysis of variance with repeated measures was conducted at each dose. At 0.3 mg/kg/infusion, there was no difference between the groups. At 0.4 mg/kg/infusion, there was a main effect of Group, F_{1, 19}=12.27, p<0.0024; an effect of Day, F_{4, 19}=2.92, p<0.0026; and a Group by Day interaction, F_{4, 19}=3.53, p<0.011. Post hoc pair wise comparisons indicated that OVX+ EB > OVX+OIL group (p<0.001). At 0.5 mg/kg/infusion of cocaine, there was a main effect of Group, F_{1 , 19}=4.84, p<0.04; an effect of Day, F_{4 ,19}=6.08, p<0.0003; but no Group by Day interaction, F_{4 ,19}=0.25. Post hoc pair wise comparisons indicated that OVX+ EB> OVX+OIL group (p<0.001). There were no group differences in the number of nose pokes in the inactive hole during any test sessions. *denotes a significant effect of EB on progressive ratio responding as indicated above.