Effects of acute restraint and unpredictable chronic mild stress on brain corticotrophin releasing factor mRNA in the elevated T-maze

Abstract

Corticotrophin releasing factor (CRF) modulates stress/anxiety-related responses. Previous studies showed that exposure to acute restraint and unpredictable chronic mild stress (UCMS) facilitates elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. This study verified the role of CRF in the modulation of ETM avoidance and escape reactions, in unstressed rats and in animals exposed to acute restraint or to UCMS, by quantifying CRF mRNA concentrations in stress/anxiety-related brain regions, through semiquantitative in situ hybridization. Results showed that stress exposure altered CRF mRNA in regions related to the modulation of stress/anxiety: the cingulate cortex, the hippocampus, the paraventricular and dorsomedial hypothalamus, the medial and central amygdalas, the dorsal region of the dorsal raphe (dDR) and the ventrolateral periaqueductal gray. A regression analysis showed that the anxiogenic-like effects observed in acute restraint animals were particularly associated to increases in CRF mRNA in the paraventricular hypothalamus, medial and central amygdalas and dDR. On the other hand, anxiogenic-like effects observed after UCMS exposure are associated to increases in CRF mRNA in the medial and central amygdalas, in the BNST and in the ventrolateral periaqueductal grey. This observation suggests important differences in the neurocircuitry that mediates responses to acute and chronic stress exposure. CRF mRNA in regions traditionally related to the modulation of panic reactions (the dorsal periaqueductal grey and the lateral wings of the dorsal raphe) were not observed, what might explain the absence of panicogenic-like effects of stress exposure. These results contribute to a better understanding of the role played by CRF in stress/anxiety-related responses.