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

Psychopharmacology (Berl). 2014 Sep;231(17):3351-64. doi: 10.1007/s00213-014-3539-9. Epub 2014 Apr 13.


Rationale: Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users.

Objectives: We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors.

Methods: Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration.

Results: EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident-intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration.

Conclusions: The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.

MeSH terms

  • Agonistic Behavior / drug effects
  • Anhedonia / drug effects
  • Animals
  • Cerebral Cortex / metabolism
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Depression / chemically induced
  • Depression / psychology
  • Drug Combinations
  • Ethinyl Estradiol / pharmacology
  • Female
  • Levonorgestrel / pharmacology
  • Maze Learning / drug effects
  • Motivation / drug effects*
  • Pregnanolone / antagonists & inhibitors*
  • Pregnanolone / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sexual Behavior, Animal / drug effects*
  • Social Behavior*
  • Swimming / psychology


  • Contraceptives, Oral, Hormonal
  • Drug Combinations
  • ethinyl estradiol, levonorgestrel drug combination
  • Ethinyl Estradiol
  • Levonorgestrel
  • Pregnanolone