Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part II. Regulatory mechanisms.
In the companion paper, we showed that the spontaneous firing activity of DRN 5-HT neurons is significantly higher in male (M) than in freely cycling female (CF) rats. Moreover, during pregnancy, it increased in parallel to circulating levels of progesterone, peaking at day 17 of pregnancy (P17). In this second part, we assessed the role of three regulatory mechanisms potentially involved in these modifications of the 5-HT neurons firing activity. During pregnancy, the ED(50) for the response to LSD was decreased by about 70%, indicating a partial desensitization of 5-HT(1A) autoreceptors, which is consistent with the 5-HT neurons higher firing activity. The GABAergic tonic inhibition of 5-HT neurons was assessed using the responses to GABA, bicuculline and isoniazid. Together, they indicate a lower GABAergic tonic inhibition in males and P17 as compared to CF, which is in agreement with their greater 5-HT neurons firing rate. Finally, the efficacy of the long feedback loop, involving postsynaptic 5-HT(1A) receptors, did not seem affected by gender, ovariectomy or pregnancy since the response to systemic 8-OH-DPAT was similar. These results constitute strong evidence of mechanisms by which gender and hormonal fluctuations can modulate the 5-HT neurons function and influence vulnerability to mood disorders.
Klink
Ruby
R
McGill University, Department of Psychiatry, 1033 Pine Avenue West, Montréal, Québec, Canada H3A 1A1.
Robichaud
Malika
M
Debonnel
Guy
G
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009474:Neurons / Q000502:physiology*; D010052:Ovariectomy; D011247:Pregnancy; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin