The progesterone metabolite allopregnanolone potentiates GABA(A) receptor-mediated inhibition of 5-HT neuronal activity.
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.
Kaura
Vikas
V
Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, NE2 4HH, UK.
Ingram
Colin D
CD
Gartside
Sarah E
SE
Young
Allan H
AH
Judge
Sarah J
SJ
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011280:Pregnanolone / Q000097:blood / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors
D000777:Anesthetics; D018755:GABA Agonists; D007555:Isoxazoles; D011963:Receptors, GABA-A; D009118:Muscimol; D012701:Serotonin; D011374:Progesterone; D011280:Pregnanolone; C015542:gaboxadol