Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress

Kathleen R. Melia, Andrey E. Ryabinin, Richard Schroeder, Floyd E. Bloom, Michael C. Wilson

Research output: Contribution to journalArticlepeer-review

322 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5929-5938
Number of pages10
JournalJournal of Neuroscience
Issue number10
StatePublished - Oct 1994
Externally publishedYes


  • adrenalectomy
  • c-fos
  • habituation
  • immediate early genes
  • restraint stress
  • swim stress

ASJC Scopus subject areas

  • Neuroscience(all)


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