Monoaminergic activity in subregions of Raphé nuclei elicited by prior stress and the neuropeptide corticotropin-releasing factor

Cliff H. Summers, J. L. Kampshoff, P. J. Ronan, C. A. Lowry, A. A. Prestbo, W. J. Korzan, K. J. Renner

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Corticotropin-releasing factor (CRF) coordinates neuroendocrine responses to stressful stimuli; one mechanism through which CRF may modulate hypothalamic-pituitary-adrenal axis activity is via actions on neuromodulatory systems such as serotonergic systems. Recent electrophysiological studies and the distribution of CRF receptors within midbrain and pontine raphé nuclei suggest that stress and CRF may have actions on topographically organized subpopulations of serotonergic neurones. We compared the effects of vehicle or intracerebroventricular r/hCRF injections (0, 0.1, 1 or 10 μg) in rats previously maintained in home cages or restrained for 1h, 24h before injection, on monoamine and monoamine metabolite tissue concentrations in the dorsal (lateral wings, rostral midline, caudal midline), median (rostral, caudal) and interfascicular raphé subdivisions of the midbrain and pontine raphé nuclei, using brain microdissection and high-performance liquid chromatography with electrochemical detection. At the lowest dose studied (0.1 μg), CRF infusions in previously stressed rats decreased 5-hydroxytryptophan (5-HTP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations only within the rostral median raphé nucleus. At higher doses, CRF infusions in previously stressed rats increased tissue concentrations of 5-HTP, serotonin (5-HT), or the serotonin metabolite, 5-HIAA, within rostral (but not caudal) regions of the median and dorsal raphé nuclei. By contrast, restraint stress alone had no effect on tissue concentrations of 5-HTP, 5-HT or 5-HIAA measured 24h later in any subdivision, while CRF injections in rats not previously exposed to restraint stress, with few exceptions, also had no effect. These results suggest that the effects of CRF on serotonergic function are context-dependent, dose-dependent, and regionally specific within subdivisions of the brainstem raphé nuclei.

Original languageEnglish (US)
Pages (from-to)1122-1133
Number of pages12
JournalJournal of Neuroendocrinology
Issue number12
StatePublished - Dec 2003
Externally publishedYes


  • CRF
  • Dopamine
  • Norepinephrine
  • Raphé
  • Restraint
  • Serotonin
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience


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