The progesterone metabolite allopregnanolone potentiates GABA(A) receptor-mediated inhibition of 5-HT neuronal activity

Eur Neuropsychopharmacol. 2007 Jan 15;17(2):108-15. doi: 10.1016/j.euroneuro.2006.02.006. Epub 2006 Mar 6.

Abstract

The dorsal raphe nucleus (DRN) is the origin of much of the 5-HT innervation of the forebrain. The activity of DRN 5-HT neurons is regulated by a number of receptors including GABA(A) and 5-HT(1A) inhibitory receptors and by excitatory alpha(1)-adrenoceptors. Using in vitro electrophysiological recording we investigated the action of progesterone and its metabolite, allopregnanolone on receptor-mediated responses of DRN 5-HT neurons. Neither allopregnanolone nor progesterone affected the alpha(1)-adrenoceptor agonist-induced firing. Allopregnanolone also had no effect on the inhibitory response to 5-HT. However, allopregnanolone significantly potentiated the inhibitory responses to GABA(A) receptor agonists. Progesterone did not enhance GABA(A) receptor-meditated inhibitory responses. Thus, the neuroactive metabolite of progesterone, allopregnanolone, has the ability to cause potentiation of GABA(A)-mediated inhibition of DRN 5-HT neurons. This effect on 5-HT neurotransmission may have relevance for mood disorders commonly associated with reproductive hormone events, such as premenstrual dysphoric disorder and postpartum depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Analysis of Variance
  • Anesthetics / pharmacology*
  • Animals
  • Drug Interactions
  • Female
  • GABA Agonists / pharmacology
  • In Vitro Techniques
  • Isoxazoles / pharmacology
  • Muscimol / pharmacology
  • Neural Inhibition / drug effects*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pregnanolone / blood
  • Pregnanolone / pharmacology*
  • Progesterone / metabolism*
  • Raphe Nuclei / cytology
  • Rats
  • Receptors, GABA-A / physiology*
  • Serotonin / pharmacology
  • Time Factors

Substances

  • Anesthetics
  • GABA Agonists
  • Isoxazoles
  • Receptors, GABA-A
  • Muscimol
  • Serotonin
  • Progesterone
  • Pregnanolone
  • gaboxadol