title: Chronic stress produces enduring decreases in novel stress-evoked c-fos mRNA expression in discrete brain regions of the rat.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237-0506, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Ostrander
authors.forename: Y M
authors.initials: YM
authors.lastname: Ulrich-Lai
authors.forename: D C
authors.initials: DC
authors.lastname: Choi
authors.forename: J N
authors.initials: JN
authors.lastname: Flak
authors.forename: N M
authors.initials: NM
authors.lastname: Richtand
authors.forename: J P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone