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

Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK, s.j.judge{at}ncl.ac.uk

Colin D. Ingram

Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK

Sarah E. Gartside

Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK

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 1-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 5-HT neurones, with increased 1-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.

Key Words: adrenalectomy • 1-adrenoceptor • 5-HT1A autoreceptor • dorsal raphe nucleus • electrophysiology • rat

Journal of Psychopharmacology, Vol. 18, No. 4, 475-483 (2004)
DOI: 10.1177/0269881104047274


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