Journal
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
Volume 12, Issue 6, Pages 469-477Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10253890802641966
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Funding
- NIH [DA016466, DK067820, MH049698, MH069725, AG012962, DA016778]
- Department of Veterans Affairs Medical Research Service
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [F32DK067820] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH069725, R29MH049698, R01MH069860, R01MH049698] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG012962] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA016778, F32DA016466] Funding Source: NIH RePORTER
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Chronic stress produces numerous adaptations within the hypothalamic-pituitary-adrenal (HPA) axis that persist well after cessation of chronic stress. We previously demonstrated profound attenuation of HPA axis responses to novel environment 4-7 days following chronic stress. The present study tests the hypothesis that this HPA axis hyporesponsivity is associated with reductions in stress-evoked c-fos mRNA expression, a marker of neuronal activation, in discrete brain regions. Adult male Sprague-Dawley rats underwent 1 week of chronic variable stress (CVS), with unhandled rats serving as controls. Independent groups of control and CVS rats were exposed to novel environment at 16 h, 4 days, 7 days, or 30 days after CVS. Marked reductions of c-fos mRNA expression in the CVS group persisted for at least 30 days within the paraventricular nucleus of the hypothalamus, and for at least 1 week in rostroventrolateral septum and lateral hypothalamus. Lower levels of c-fos mRNA expression were observed at 16 h recovery in the ventrolateral medial preoptic area, basolateral amygdala, anterior cingulate cortex, and prelimbic cortex. The results demonstrate long-term alterations in neuronal activation within neurocircuits critical for regulation of physiological and psychological responses to stressors.
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