Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats

Allopregnanolone (AP) is a progesterone (P) metabolite that facilitates social and sexual behavior in rats. We have demonstrated that chronic treatment with ethinyl estradiol and levonorgestrel (EE/LNG), two of the compounds most frequently used in hormonal contraceptives, decreases brain AP and P levels in female rats. We now evaluate whether this decrease in AP levels induced by EE/LNG altered social and sexual behavior. Female rats were orally treated with a combination of EE 0.030 mg and LNG 0.125 mg once a day for 4 weeks and underwent behavioral tests 24 h after the last treatment. EE/LNG treatment decreased frequency of dominance score, agonistic behaviors delivered and social investigation, and increased duration of social inactivity in the resident-intruder test for social behavior. In the paced mating test, EE/LNG-treated rats showed no proceptive behaviors, a measure of sexual motivation, but receptivity was similar to that of controls. P administration 4 mg/kg, 4 h before the paced mating test, increases brain AP levels and proceptivity in EE/LNG-treated rats, while finasteride administration (a 5alpha-reductase inhibitor, 50 mg/kg) 2 h before P, decreases AP levels and almost completely abolishes the increase in proceptivity induced by P. Thus, the decrease in AP levels induced by EE/LNG is associated with decreased social behaviors and sexual motivation. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.