Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity.
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 alpha1-adrenoceptor agonist phenylephrine (1-11 microM) was significantly greater in the 2% group compared to the 70% group. By contrast, the inhibitory response to 5-HT (10-50 microM) 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 alpha 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.
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
Ingram
Colin D
CD
Gartside
Sarah E
SE
D000315:Adrenalectomy; D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; D003345:Corticosterone