Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats

J Neuroendocrinol. 2005 Mar;17(3):179-85. doi: 10.1111/j.1365-2826.2005.01292.x.


Women are twice as likely to suffer from mood disorders than men. Moreover, a growing body of evidence suggests a reciprocal modulation between sex steroids and the serotonin (5-HT) system. A previous study from our laboratory has shown that the progesterone metabolites 5beta-pregnane-3,20-dione (5beta-DHP) and 5alpha-pregnan-3alpha-ol,20-one (3alpha,5alpha-THP), as well as dehydroepiandrosterone (DHEA), increase the firing activity of dorsal raphe nucleus (DRN) 5-HT neurones in female rats. The present study was undertaken to assess the effects of these steroids in male rats, as well as the effects of testosterone and 17beta-oestradiol (17beta-E) in both sexes, and finally to evaluate gender differences in the modulation of the 5-HT neuronal firing activity by these different neuroactive steroids. Male rats were treated i.c.v., for 7 days, with a dose of 50 microg/kg/day of one of the following steroids: progesterone, 5beta-DHP, 3alpha,5alpha-THP, DHEA, testosterone, 17beta-hydroxy-5alpha-androstan-3-one (5alpha-DHT) and 17beta-E. Some rats also received a 3-day administration of testosterone (50 microg/kg/day, i.c.v). Females were treated in the same fashion with testosterone and 17beta-E. Extracellular unitary recordings of 5-HT neurones, obtained in vivo in the DRN of these rats, revealed that testosterone and 17beta-E increased the firing activity of 5-HT neurones in both males and females. In males, the effect of testosterone could already be seen after 3 days of treatment. Neither castration nor any treatment with other steroids significantly modified the firing rate of male 5-HT neurones. Taken together with previous findings, the results of the present study indicate both similarities and differences between sexes in the modulation of 5-HT neurones by some steroids. This could prove important in understanding gender differences in mood disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Analysis of Variance
  • Animals
  • Electrophysiology
  • Estradiol / administration & dosage
  • Estradiol / physiology*
  • Female
  • Gonadal Steroid Hormones / administration & dosage
  • Gonadal Steroid Hormones / physiology
  • Injections, Intraventricular
  • Male
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Raphe Nuclei / cytology
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Sex Factors
  • Testosterone / administration & dosage
  • Testosterone / physiology*


  • Gonadal Steroid Hormones
  • Serotonin
  • Testosterone
  • Estradiol