TY - JOUR T1 - Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5929 LP - 5938 DO - 10.1523/JNEUROSCI.14-10-05929.1994 VL - 14 IS - 10 AU - KR Melia AU - AE Ryabinin AU - R Schroeder AU - FE Bloom AU - MC Wilson Y1 - 1994/10/01 UR - http://www.jneurosci.org/content/14/10/5929.abstract N2 - 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. ER -