Reciprocal cross-desensitization of locus coeruleus electrophysiological responsivity to corticotropin-releasing factor and stress.
While acutely administered corticotropin-releasing factor (CRF) and acute stress each activate neurons of the locus coeruleus (LC), desensitization to both develops with repeated treatment. The present experiments were designed to investigate whether cross-desensitization develops between CRF and stress. Because acute hemodynamic stress caused by intravenous infusion of sodium nitroprusside increases LC electrophysiological discharge rate via a CRF-dependent mechanism, it was hypothesized that repeated CRF administration would cause desensitization to the effect of this stressor on LC. For a complementary experiment, it was hypothesized that repeated stress, which presumably results in the repeated release of endogenous CRF, would result in desensitization to subsequent exogenous CRF. The results of the first experiment showed that repeated intracerebroventricular (i.c.v.) administration of CRF caused a significant attenuation of the sodium nitroprusside-induced increase in LC discharge rate seen in naive rats, although this pretreatment actually potentiated the decrease in blood pressure produced by sodium nitroprusside. In the second experiment, either one or eight sessions of white-noise stress attenuated the effect of CRF on LC activity 24 h after the last stress exposure, and this attenuation was more pronounced following eight sessions of stress than following one session. In a test of the specificity of this effect, stress-induced desensitization did not generalize to the LC electrophysiological response to clonidine (i.c.v.). One week following the last of eight sessions of stress, LC responsivity to CRF had recovered to control levels. These experiments demonstrate reciprocal cross-desensitization between CRF and stress using LC electrophysiological responsivity as an assay. This modifiability of the interaction between CRF and the LC may represent the operation of mechanisms mediating adaptive responding to stress.
Conti
L H
LH
Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla 92093, USA.
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S L
SL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004594:Electrophysiology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*
D000959:Antihypertensive Agents; D009599:Nitroprusside; D003346:Corticotropin-Releasing Hormone; D003000:Clonidine