Alterations in corticoptropin-releasing factor-like immunoreactivity in discrete rat brain regions after acute and chronic stress

Phillip B. Chappell, Mark A. Smith, Clinton D. Kilts, Garth Bissette, James Ritchie, Carl Anderson, Charles B. Nemeroff

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424 Scopus citations


Corticotropin releasing factor (CRF) may regulate endocrine, autonomic, and behavioral responses to stress. Evidence indicates that CRF-like immunoreactivity (CRF-LI) is widely distributed throughout the CNS. In this study, the distribution of CRF-LI was determined in 36 rat brain regions by combined radioimmunoassay-micropunch dissection techniques and the effect of stress on CRF-LI was investigated, using a chronic stress model that induces endocrine changes in rats similar to those seen in depressed humans. A control group of rats was handled daily. An acute stress group was subjected to 3 hr of immobilization at 4°C, while a chronic stress group was exposed to unpredictable stressors. Thirty-six brain regions were microdissected by the technique of Palkovits and assayed for CRF-LI, using a specific antiserum to ovine CRF. CRF-LI was detected in most regions. In controls, the highest concentrations were found in arcuate nucleus/median eminence, the hypothalamic paraventricular (PVN) nucleus, and the periventricular nucleus. The next highest levels were found in the raphe nuclei and dorsal vagal complex. CRF-LI was well represented in the locus coeruleus (LC); in the central, cortical, and medial amygdaloid nuclei; and in the bed nucleus of the stria terminalis. Low concentrations occurred in the hippocampus and cerebrocortical regions. Appreciable concentrations were detected in midbrain and brain stem regions. Acute stress reduced CRF-LI in the arcuate nucleus/median eminence (ME) (by 52%) and in the median preoptic (MPO) nucleus (by 32%) and doubled its concentration in the locus coeruleus. Chronic stress produced changes similar to those of acute stress in the arcuate nucleus/median eminence (ME) and coeruleus, while significantly increasing CRF-LI in the anterior hypothalamic and periventricular nuclei and significantly decreasing CRF-LI in the dorsal vagal complex (DVC). These results suggest that stress alters CRF-LI in brain regions that have been implicated in the CNS response to stress.

Original languageEnglish (US)
Pages (from-to)2908-2914
Number of pages7
JournalJournal of Neuroscience
Issue number10
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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