title: Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress.
abstract: Acute exposure to stress leads to activation of the pituitary-adrenal axis (PA-axis) while repeated exposure to a homotypic stressor generally results in habituation of this response. Previous studies suggested that such habituation is largely due to changes in afferents of the PA-axis. To examine where within these afferents habituation occurs, we studied the effect of acute and repeated exposure to 2 hr restraint stress on expression of c-fos mRNA, as a marker of altered neuronal activity, in brain regions previously shown to influence the activity of the PA-axis. Acute restraint stress increased expression of c-fos mRNA in cortex, hippocampus, hypothalamus, septum, and brainstem. In contrast, the effect of restraint stress on c-fos expression in the aforementioned brain regions was much smaller in animals restrained once daily for 4 d, and nonexistent in animals restrained once daily for 9 d. A similar pattern of induction and habituation of jun-B, but not zif-268, c-jun, or jun-D mRNA expression, was observed in the cortex of animals exposed to acute versus repeated restraint stress. The habituation of c-fos responses was stressor specific: exposure of restraint-adapted animals to a novel (20 min swim) stress produced an increase in levels of c-fos mRNA in every examined brain region comparable to that seen in animals exposed to this stressor for the first time. Adrenalectomy did not alter the pattern of c-fos expression induced by acute and repeated restraint stress. Therefore, activation and habituation of these c-fos responses are independent of changes in circulating levels of corticosterone.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: K R
authors.initials: KR
authors.lastname: Melia
authors.forename: A E
authors.initials: AE
authors.lastname: Ryabinin
authors.forename: R
authors.initials: R
authors.lastname: Schroeder
authors.forename: F E
authors.initials: FE
authors.lastname: Bloom
authors.forename: M C
authors.initials: MC
authors.lastname: Wilson
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000502:physiology; D001923:Brain Chemistry; D003345:Corticosterone / Q000097:blood*; D015870:Gene Expression / Q000502:physiology*; D016762:Genes, fos / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*; D013550:Swimming / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone