Cytokine involvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety.
Cytokine involvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety.
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DOI：
10.1016/j.bbi.2011.02.018
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发表时间：
2011-06
影响因子：
15.1
通讯作者：
Breese, George R.
中科院分区：
文献类型：
--
作者：
Knapp, Darin J.;Whitman, Buddy A.;Wills, Tiffany A.;Angel, Robert A.;Overstreet, David H.;Criswell, Hugh E.;Ming, Zhen;Breese, George R.
关键词：
压力已被证明会促进乙醇戒断引起的焦虑。考虑到相关的复发风险，定义压力产生此类作用的神经生物学机制非常重要。虽然 CRF 长期以来一直被认为与压力的作用有关，但目前的结果表明，压力会升高大鼠大脑中的细胞因子 TNFα，从而暗示细胞因子与压力的影响有关。为了支持这一观点，先前将 TNFα 显微注射到大鼠中央杏仁核 (CeA) 会促进乙醇戒断引起的焦虑，这种反应不能归因于血浆皮质酮的增加。为了测试细胞因子和 CRF 之间可能存在的相互作用，在重复给予 TNFα 或 MCP-1/CCL2 之前给予 CRF1 受体拮抗剂 (SSR125543)，可降低戒断引起的焦虑程度。这一发现为细胞因子作用依赖于 CRF 提供了证据。此外，通过使用 MEK 抑制剂 SL327 治疗乙醇之前的重复压力暴露，可以降低压力对戒断引起的焦虑的敏化作用。与具有不同于神经免疫作用的神经介导功能的细胞因子一致，TNFα增加了CeA神经元的放电率和GABA释放。因此，神经胶质和神经元功能的相互作用被认为有助于应激和慢性乙醇的相互作用。中断这种潜在的神经胶质-神经元相互作用可以提供一种新的方法来改变由压力引起的情绪状态的发展，从而预测酗酒者的复发。
Stress has been shown to facilitate ethanol withdrawal-induced anxiety. Defining neurobiological mechanisms through which stress has such actions is important given the associated risk of relapse. While CRF has long been implicated in the action of stress, current results show that stress elevates the cytokine TNFα in the rat brain and thereby implicates cytokines in stress effects. In support of this view, prior TNFα microinjection into the central amygdala (CeA) of rats facilitated ethanol withdrawal-induced anxiety—a response that could not be attributed to an increase in plasma corticosterone. To test for a possible interaction between cytokines and CRF, a CRF1-receptor antagonist (SSR125543) administered prior to the repeated administration of TNFα or MCP-1/CCL2 reduced the magnitude of the withdrawal-induced anxiety. This finding provided evidence for cytokine action being dependent upon CRF. Additionally, the sensitizing effect of stress on withdrawal-induced anxiety was reduced by treating the repeated stress exposure prior to ethanol with the MEK inhibitor SL327. Consistent with cytokines having a neuromediator function distinct from a neuroimmune action, TNFα increased firing rate and GABA release from CeA neurons. Thus, an interaction of glial and neuronal function is proposed to contribute to the interaction of stress and chronic ethanol. Interrupting this potential glial-neuronal interaction could provide a novel means by which to alter the development of emotional states induced by stress that predict relapse in the alcoholic.
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影响因子：
13.5
作者：
Breese, George R.;Sinha, Rajita;Heilig, Markus
通讯作者：
Heilig, Markus
影响因子：
3
作者：
Hauger, Richard L.;Risbrough, Victoria;Dautzenberg, Frank M.
通讯作者：
Dautzenberg, Frank M.
影响因子：
7.6
作者：
Breese, GR;Knapp, DJ;Overstreet, DH
通讯作者：
Overstreet, DH
DOI：
10.1007/bf01065866
发表时间：
1993-01-01
期刊：
Psychiatric Quarterly (New York)
影响因子：
--
作者：
Brady, Kathleen T.;Lydiard, R. Bruce
通讯作者：
Lydiard, R. Bruce
影响因子：
5.3
作者：
Alfonso-Loeches, Silvia;Pascual-Lucas, Maya;Guerri, Consuelo
通讯作者：
Guerri, Consuelo