Effects of environmental and pharmacological stressors on c-fos and corticotropin-releasing factor mRNA in rat brain:: Relationship to the reinstatement of alcohol seeking
Effects of environmental and pharmacological stressors on c-fos and corticotropin-releasing factor mRNA in rat brain:: Relationship to the reinstatement of alcohol seeking
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DOI：
10.1016/j.neuroscience.2005.10.062
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Lê, AD
中科院分区：
文献类型：
--
作者：
Funk, D;Li, Z;Lê, AD
我们观察到不同的应激源在恢复大鼠酒精寻找的能力上存在显著的异质性。在我们测试的应激源中，只有环境应激源FootShock和药物应激源育亨宾能诱导恢复。压力源之间存在这种差异的原因尚不清楚。这里提出的实验的目的是确定这些行为差异背后的神经解剖学基础。为此，我们使用c-fos和促肾上腺皮质激素释放因子(CRF)的原位杂交技术，评估了在诱导酒精寻求恢复过程中有效的应激源是否激活了与那些无效的不同的神经通路。c-fos是神经元激活的标志，促肾上腺皮质激素释放因子(CRF)是一种应激相关肽，我们已经证明，应激相关肽对足底电击导致的酒精寻求恢复至关重要。将大鼠暴露于环境应激源足部电击、束缚或社交失败，或药物应激源育亨宾或FG-7142，会增加大脑中先前被证明对应激源有反应的一些区域中c-fos和CRF的mRNAs水平。我们发现，应激源对与酒精和其他滥用药物的奖赏效应相关的脑区c-fos和CRF mRNA的区域特异性影响。我们之前已经证明了两种在诱导酒精寻求恢复方面有效的应激源，足底电击和育亨宾，诱导了伏核外壳以及杏仁基底外侧核和中央杏仁核的c-fos mRNA。这两种应激源也诱导了终纹床核背侧区域CRF基因的表达。综上所述，这些结果提供了证据，表明这些区域的活动可能参与了由这些应激源诱导的酒精寻求的恢复。这些结果也与先前证实的终纹背侧床核CRIF神经元在应激诱导的酒精寻求恢复中的作用是一致的。(C)2005年由爱思唯尔有限公司代表IBRO出版。
We have observed marked heterogeneity among different stressors in their ability to reinstate alcohol seeking in rats. Of the stressors we have tested, only the environmental stressor footshock and the pharmacological stressor yohimbine induce reinstatement. The reasons for such differences among stressors are not known. The purpose of the experiments presented here is to determine the neuroanatomical substrates that underlie these behavioral differences. To this end, we assessed whether stressors effective in inducing reinstatement of alcohol seeking activate a different set of neuronal pathways than do those that are ineffective, using the technique of in situ hybridization of the mRNAs for c-fos, a marker of neuronal activation, and corticotropin-releasing factor (CRF), a stress-related peptide we have shown to be critical to footshock-inuced reinstatement of alcohol seeking. Exposure of rats to the environmental stressors footshock, restraint or social defeat, or the pharmacological stressors yohimbine or FG-7142 increased levels of the mRNAs for c-fos and CRF in the brain in a number of areas previously shown to be responsive to stressors. We found regionally specific effects of the stressors on c-fos and CRF mRNA in brain regions associated with the rewarding effects of alcohol and other abused drugs. The two stressors we have previously shown to be effective in inducing reinstatement of alcohol seeking, footshock and yohimbine, induced c-fos mRNA in the shell of the nucleus accumbens, and the basolateral and central amygdalar nuclei. These two stressors also induced CRF mRNA in the dorsal region of the bed nucleus of the stria terminalis. Taken together, these results provide evidence that activity in these regions may be involved in the reinstatement of alcohol seeking induced by these stressors. These results are also in keeping with the previously demonstrated role of CRIF neurons in the dorsal bed nucleus of the stria terminalis in the reinstatement of alcohol seeking induced by stress. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.