Springer Verlag, Psychopharmacology, 17(231), p. 3351-3364
DOI: 10.1007/s00213-014-3539-9
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The progesterone metabolite allopregnanolone is a neurosteroid that exerts a rapid non genomic effect on neuronal excitability through a direct modulation of the gamma-aminobutyric acid type A receptor (GABA-A). It has been shown that allopregnanolone facilitates social and sexual behavior in rodents, which evoke further increases in brain allopregnanolone concentrations. Thus, systemic or local allopregnanolone administration in the hypothalamus or midbrain promotes sexual behavior while block of progesterone metabolism through a 5alpha-reductase inhibitor (finasteride) reduces proceptivity and receptivity compared to control animals. We have previously demonstrated that chronic treatment with a combination of ethinylestradiol and levonorgestrel (EE/LNG), two of the compounds most frequently used in hormonal contraceptives, decreases brain concentrations of allopregnanolone and progesterone. Here we evaluate whether the reduction in the brain concentrations of allopregnanolone induced by EE/LNG treatment alters social and sexual behavior in female rats. Female rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for four weeks and were sacrificed or subjected to the behavioral tests 24 hours after the last treatment. Social behavior was assessed using the resident-intruder test, while sexual receptivity and motivation were assessed using paced and non-paced mating tests. Progesterone (4 mg/kg) was administered subcutaneously 4 hours before the paced mating test; finasteride (50 mg/kg) was administered subcutaneously 2 hours before progesterone administration. In the resident-intruder test, EE/LNG treatment specifically affected social and agonistic behavior by decreasing the frequency of the dominance score (-114%, p