title: Stress-induced sensitization of CRH-ir but not P-CREB-ir responsivity in the rat central nervous system.
abstract: There is some evidence that a traumatic life event can induce long-term alterations in corticotropin-releasing hormone (CRH) producing neurons in humans, which may play a role in the pathophysiology of anxiety disorders, including post-traumatic stress disorder (PTSD). To study the long-term effects of a traumatic event on brain CRH-immunoreactivity (CRH-ir) and phospho-cAMP response element binding protein-immunoreactivity (P-CREB-ir), rats were exposed to a single session of foot shocks (preshocked) or no shocks (control). Two weeks later half of the control rats and half of the preshocked rats received an electrified prod in the home cage for 15 min and behavior was recorded. Fifteen minutes after the removal of the prod rats were perfused and brain sections were stained for CRH-ir and P-CREB-ir. There was no basal difference between preshocked and control rats in brain CRH-ir and P-CREB-ir. Exposure to the electrified prod induced a significant increase in CRH-ir in the paraventricular nucleus of the hypothalamus, the median eminence and the central amygdala in preshocked rats, but not in control rats. The electrified prod increased the number of P-CREB-ir neurons in the paraventricular nucleus of the hypothalamus and the locus coeruleus, but the preshock experience did not affect this response. In an additional experiment with a similar design plasma hormone levels were measured 14 days after the foot shocks. The preshock experience sensitized the shock prod-induced ACTH and corticosterone response. No behavioral differences between preshocked and control rats were found during the shock prod tests. We suggest that long-term stress-induced changes in neuropeptide dynamics of CRH-ir neurons may play a role in long-term stress-induced neuroendocrine sensitization.
authors.affiliation: Division of Pharmacology and Anatomy, Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, The Netherlands. a.w.bruijnzeel@med.uu.nl
authors.forename: A W
authors.initials: AW
authors.lastname: Bruijnzeel
authors.forename: R
authors.initials: R
authors.lastname: Stam
authors.forename: J C
authors.initials: JC
authors.lastname: Compaan
authors.forename: V M
authors.initials: VM
authors.lastname: Wiegant
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004558:Electric Stimulation / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone