PATTERN AND TIME-COURSE OF IMMEDIATE-EARLY GENE-EXPRESSION IN RAT-BRAIN FOLLOWING ACUTE STRESS

The pattern and time course of brain activation in response to acute s wim and restraint stress were examined in the rat by in situ hybridiza tion using complementary RNA probes specific for transcripts encoding the products of the immediate early genes c-fos, c-jun and zif/268. A widespread pattern of c-fos messenger RNA expression was detected in r esponse to these stressors; surprisingly, the expression patterns were substantially similar following both swim and restraint stress. A dra matic induction of c-fos messenger RNA was observed in numerous neo- a nd allocortical regions, the lateral septal nucleus, the hypothalamic paraventricular and dorsomedial nuclei, the anterior hypothalamic area , the lateral portion of the retrochiasmatic area, the medial and cort ical amygdaloid nuclei, the periaqueductal gray, and the locus coerule us; however, a prominent induction of c-fos was also seen in numerous additional subcortical and brainstem regions. Although not as widely e xpressed in response to stress as c-fos, induction of zif/268 messenge r RNA was also detected throughout many brain areas; these regions wer e largely similar to those in which c-fos was induced, although in a n umber of regions zif/268 was expressed in regions devoid of c-fos mess enger RNA. Few brain areas showed increased expression of c-jun follow ing stress; these regions also showed induction of c-fos and/or zif/26 8. The time courses of expression of all three immediate early genes w ere similar, with peak levels observed at the 30 or 60 min time point, and a markedly reduced signal evident at 120 min post-stress. However , in a number of cases a delayed and/or prolonged induction was noted that may be indicative of secondary neuronal activation. A number of r ecent studies have attempted to define neural pathways which convey st ress-related information to the hypothalamic-pituitary-adrenal axis. T he present results reveal a widespread pattern of neuronal activation in response to acute swim or restraint stress. These findings may aid in the identification of stress-specific neural circuits and are thus likely to have important implications for our understanding of neurona l regulation of the stress response.