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.
Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats
Porcu P;
2013
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.