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GABA receptor modulation of 5-HT neuronal firing: characterization and effect of moderate in vivo variations in glucocorticoid levels

Lookup NU author(s): Dr Sarah Judge, Professor Colin Ingram, Dr Sasha Gartside

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Abstract

Evidence from electrophysiological studies suggests that 5-HT neuronal firing in the dorsal raphe nucleus (DRN) may be regulated by both GABA(A) and GABA(B) receptors. Here, we addressed the question of whether the activity of individual 5-HT neurons is regulated by both GABA(A) and GABA(B) receptors. In addition, we examined the concentration-response relationships of GABA(A) and GABA(B) receptor activation and determined if GABA receptor regulation of 5-HT neuronal firing is altered by moderate alterations in circulating corticosterone. The activity of 5-HT neurons in the DRN of the rat was examined using in vitro extracellular electrophysiology. The firing of all individual neurons tested was inhibited by both the GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol hydrochloride (THIP) (25microM) and the GABA(B) receptor agonist baclofen (1microM). Responses to THIP (5, 10, 25microM) and baclofen (1, 3, 10microM) were concentration dependent and attenuated by the GABA(A) and GABA(B) receptor antagonists, bicuculline (50microM) and phaclofen (200microM), respectively. To examine the effects of corticosterone on the sensitivity of 5-HT neurons to GABA receptor activation, experiments were conducted on adrenalectomized animals with corticosterone maintained for two weeks at either a low or moderate level within the normal diurnal range. These changes in corticosterone levels had no significant effects on the 5-HT neuronal response to either GABA(A) or GABA(B) recepter activation. The data indicate that the control of 5-HT neuronal activity by GABA is mediated by both GABA(A) and GABA(B) receptors and that this control is insensitive to moderate changes in circulating glucocorticoid levels.


Publication metadata

Author(s): Judge SJ, Ingram CD, Gartside SE

Publication type: Article

Publication status: Published

Journal: Neurochemistry International

Year: 2004

Volume: 45

Issue: 7

Pages: 1057-1065

Print publication date: 20/07/2004

Date deposited: 03/11/2009

ISSN (print): 0197-0186

ISSN (electronic): 1872-9754

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.neuint.2004.05.003

DOI: 10.1016/j.neuint.2004.05.003

PubMed id: 15337305


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