• neurosteroids;
  • 5-HT neurones;
  • gender differences;
  • electrophysiology;
  • depression


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 5β-pregnane-3,20-dione (5β-DHP) and 5α-pregnan-3α-ol,20-one (3α,5α-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 17β-oestradiol (17β-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 µg/kg/day of one of the following steroids: progesterone, 5β-DHP, 3α,5α-THP, DHEA, testosterone, 17β-hydroxy-5α-androstan-3-one (5α-DHT) and 17β-E. Some rats also received a 3-day administration of testosterone (50 µg/kg/day, i.c.v). Females were treated in the same fashion with testosterone and 17β-E. Extracellular unitary recordings of 5-HT neurones, obtained in vivo in the DRN of these rats, revealed that testosterone and 17β-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.