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


OBJECTIVE
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.
Price
Michelle L
ML
David Mahoney Institute Neurological Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kirby
Lynn G
LG
Valentino
Rita J
RJ
Lucki
Irwin
I
D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D004594:Electrophysiology; D008297:Male; D017551:Microdialysis; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology; D013550:Swimming; D013997:Time Factors
C113202:phenylalanyl corticotropin-releasing factor (12-41); D012701:Serotonin; D003346:Corticotropin-Releasing Hormone