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Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity

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



Circulating glucocorticoid levels vary with stress and psychiatric illness and play a potentially important role in regulating transmitter systems that regulate mood. To determine whether chronic variation in corticosterone levels within the normal diurnal range altered the control of 5-hydroxytryptamine (5-HT) neuronal activity, male rats were adrenalectomized and implanted with either a 2% or 70% corticosterone/cholesterol pellet (100 mg). Two weeks later, the regulation of 5-HT neuronal activity in the dorsal raphe nucleus was studied by in vitro electrophysiology. At this time, serum corticosterone levels approximated the low-point (2%) and mid-point (70%) of the diurnal range. The excitatory response of 5-HT neurones to the α1-adrenoceptor agonist phenylephrine (1-11 μM) was significantly greater in the 2% group compared to the 70% group. By contrast, the inhibitory response to 5-HT (10-50 μM) was significantly lower in the 2% group compared to the 70% group. Thus, chronic variation in circulating corticosterone over a narrow part of the normal diurnal range causes a shift in the balance of positive and negative regulation of B-HT neurones, with increased α1-adrenoceptor-mediated excitation and reduced 5-HT-mediated autoinhibition at lower corticosterone levels. This shift would have a major impact on control of 5-HT neuronal activity.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Journal of Psychopharmacology

Year: 2004

Volume: 18

Issue: 4

Pages: 475-483

Print publication date: 01/12/2004

ISSN (print): 0269-8811

ISSN (electronic): 1461-7285

Publisher: Sage Publications Ltd.


DOI: 10.1177/0269881104047274

PubMed id: 15582914


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