GABA(A) receptor modulation of 5-HT neuronal firing in the median raphe nucleus: implications for the action of anxiolytics.
5-HT neurones in the median raphe nucleus (MRN) are involved in anxiety and the sleep/wake cycle. Here, using in vitro electrophysiology, we examined if the firing of MRN 5-HT neurones is regulated by GABA(A) receptors. The GABA(A) receptor agonists THIP and muscimol caused concentration dependent inhibition of MRN 5-HT neurones. The GABA(A) receptor antagonist bicuculline blocked the responses to THIP and muscimol. Bicuculline alone increased the basal firing activity. Responses to THIP were enhanced by the Z hypnotic zolpidem at concentrations selective for the alpha(2)/alpha(3) subunits of the GABA(A) receptor (0.2 and 1microM) but not at a concentration selective for the alpha(1) subunit (0.02microM). Consistent with these functional data, 5-HT neurones have been shown to express the alpha(3) (but not alpha(2)) subunit. The anxiolytic effects of GABA(A) receptor modulators are reportedly mediated by alpha(3)-containing receptors. Hence the MRN 5-HT system may be a target for anxiolytic drugs.
Judge
Sarah J
SJ
Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, NE2 4HH, UK. s.j.judge@ncl.ac.uk
Young
Rachael L
RL
Gartside
Sarah E
SE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D012701:Serotonin; D001640:Bicuculline