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

J Psychopharmacol. 2004 Dec;18(4):475-83. doi: 10.1177/026988110401800404.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Circadian Rhythm / physiology
  • Corticosterone / physiology*
  • Electrophysiology
  • Male
  • Neurons / physiology*
  • Phenylephrine / pharmacology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology
  • Rats
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology*


  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Receptors, Serotonin
  • Phenylephrine
  • Serotonin
  • Corticosterone