Evidence for corticotropin-releasing factor regulation of serotonin in the lateral septum during acute swim stress: adaptation produced by repeated swimming

Psychopharmacology (Berl). 2002 Aug;162(4):406-14. doi: 10.1007/s00213-002-1114-2. Epub 2002 Jun 29.


Rationale: Swim stress decreases extracellular serotonin (5-HT) levels in the rat lateral septum, and adaptation to this effect occurs with repeated swimming. Corticotropin-releasing factor (CRF) administered into the dorsal raphe nucleus (DRN) also decreases 5-HT release in the lateral septum, suggesting that CRF may mediate the effects of swim stress.

Objectives: The hypothesis that endogenous CRF mediates the reduction of 5-HT levels in the lateral septum evoked by swim stress and is involved in the adaptation that occurs with repeated swim stress was tested.

Methods: Extracellular 5-HT levels in rat lateral septum were quantified by means of in vivo microdialysis. Extracellular single unit activity was recorded from the DRN.

Results: Intracerebroventricular (i.c.v.) administration of a CRF receptor antagonist prevented the ability of swim stress to decrease 5-HT release in the lateral septum. Prior exposure to swim stress reduced the ability of both CRF (i.c.v.) and a subsequent swim stress to decrease lateral septum 5-HT release (cross adaptation). Additionally, the effects of CRF, administered into the DRN, on DR neuronal discharge were attenuated in rats with a history of swim stress. Finally, administration of a CRF receptor antagonist (i.c.v.) between two swim stress sessions restored the neurochemical response to swim stress (i.e., 5-HT levels were reduced during the second exposure to swim).

Conclusions: Endogenous CRF modulates 5-HT transmission during acute environmental stress and is also integral to adaptation of the 5-HT response produced by repeated stress. Modulation of the 5-HT system by CRF during acute stress may underlie certain coping behaviors, while stress-induced adaptation of this effect may be involved in psychiatric manifestations of repeated stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Corticotropin-Releasing Hormone / analogs & derivatives*
  • Corticotropin-Releasing Hormone / pharmacology*
  • Corticotropin-Releasing Hormone / physiology
  • Electrophysiology
  • Male
  • Microdialysis
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Septum of Brain / drug effects
  • Septum of Brain / metabolism*
  • Serotonin / metabolism*
  • Stress, Physiological / physiopathology
  • Swimming
  • Time Factors


  • phenylalanyl corticotropin-releasing factor (12-41)
  • Serotonin
  • Corticotropin-Releasing Hormone