Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility

Ethan H. Beckley, Deborah A. Finn

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5α-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p < .05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume87
Issue number4
DOIs
StatePublished - Oct 2007

Keywords

  • Allopregnanolone
  • Behavioral despair
  • Depression
  • Finasteride
  • GABA-A receptor
  • Postpartum depression
  • Premenstrual syndrome
  • Progesterone withdrawal

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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