de Andrade José S, Céspedes Isabel C, Abrão Renata O, da Silva Joelcimar M, Ceneviva Ricardo, Ribeiro Daniel Araki, Bittencourt Jackson C, Viana Milena B
Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos, SP, Brazil.
Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP),São Paulo, SP, Brazil.
Behav Brain Res. 2018 Jan 30;337:139-150. doi: 10.1016/j.bbr.2017.09.029. Epub 2017 Sep 19.
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.
促肾上腺皮质激素释放因子（CRF）调节与应激/焦虑相关的反应。先前的研究表明，急性束缚和不可预测的慢性轻度应激（UCMS）会促进T迷宫（ETM）回避反应增强，这是一种类焦虑样效应。本研究通过半定量原位杂交技术，量化应激/焦虑相关脑区中CRF mRNA的浓度，验证了CRF在未受应激的大鼠以及暴露于急性束缚或UCMS的动物中对ETM回避和逃避反应调节中的作用。结果显示，应激暴露改变了与应激/焦虑调节相关区域的CRF mRNA水平，这些区域包括扣带回皮质、海马、室旁核和背内侧下丘脑、内侧和中央杏仁核、中缝背核背侧区域（dDR）以及腹外侧导水管周围灰质。回归分析表明，在急性束缚动物中观察到的类焦虑样效应尤其与室旁下丘脑、内侧和中央杏仁核以及dDR中CRF mRNA的增加有关。另一方面，UCMS暴露后观察到的类焦虑样效应与内侧和中央杏仁核、终纹床核以及腹外侧导水管周围灰质中CRF mRNA的增加有关。这一观察结果表明，介导对急性和慢性应激暴露反应的神经回路存在重要差异。在传统上与惊恐反应调节相关的区域（背侧导水管周围灰质和中缝背核侧翼）未观察到CRF mRNA，这可能解释了应激暴露不存在类惊恐样效应的原因。这些结果有助于更好地理解CRF在应激/焦虑相关反应中所起的作用。
