Long-term effects of a single exposure to immobilization stress on the hypothalamic-pituitary-adrenal axis: transcriptional evidence for a progressive desensitization process.
In the present work we have characterized the long-term influence of a single exposure to the stress of immobilization (IMO) on the hypothalamic-pituitary-adrenal (HPA) axis of adult rats. Rats without prior stress (control) and rats exposed to IMO for 2 h on day 1 (IMO+4wk) or on day 21 (IMO+1wk) were killed on day 28, either without stress (basal), immediately after IMO for 1 h (IMO), or 1 h after termination of IMO (post-IMO). IMO caused a strong activation of c-fos mRNA and corticotropin-releasing factor (CRF) and vasopressin (AVP) heteronuclear RNA (hnRNA) in the paraventricular nucleus of the hypothalamus in control rats; this activation was essentially maintained in the post-IMO period. The overall AVP hnRNA response to day 28 stress was not affected by prior stress. Post-IMO c-fos mRNA and CRF hnRNA levels were lower in previously stressed rats, as compared with controls. Whereas the effect of prior IMO on both peripheral HPA hormones and c-fos mRNA was maximal in IMO+1wk rats, the effect of prior stress on CRF hnRNA was only observed in IMO+4wk rats. The present data indicate that prior single IMO triggers a process of desensitization of the HPA responsiveness to IMO over the course of the following weeks. Although the various components of the HPA axis were modified in the same direction, a clear temporal dissociation was found among them, revealing the fine tuning of stress-induced activation of the HPA axis.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System; D007103:Immobilization / Q000009:adverse effects*; D017403:In Situ Hybridization; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000503:physiopathology; D010913:Pituitary-Adrenal System; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D013995:Time; D014158:Transcription, Genetic; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone