Medial habenula cholinergic signaling regulates cocaine-associated relapse-like behavior.
Medial habenula cholinergic signaling regulates cocaine-associated relapse-like behavior.
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DOI：
10.1111/adb.12605
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发表时间：
2019-05
影响因子：
3.4
通讯作者：
Wood MA
中科院分区：
文献类型：
--
作者：
López AJ;Jia Y;White AO;Kwapis JL;Espinoza M;Hwang P;Campbell R;Alaghband Y;Chitnis O;Matheos DP;Lynch G;Wood MA
即使在长期禁欲之后，复发倾向也是物质使用障碍的一个关键特征。众所周知，复发和类似复发的行为在一定程度上是由于重新暴露于与药物相关的线索而引起的。然而，虽然神经回路中导致复发的许多关键节点已经被识别和研究，但缺乏对驱动寻药行为恢复的网络的完整描述。可以进一步了解复发机制的一个区域是缰核复合体，这是一个由外侧和内侧 (MHb) 亚结构组成的上丘脑区域，每个亚结构都有独特的细胞和目标群体。尽管 MHb 在脊椎动物物种中保存完好，但其功能尚不清楚。最近的研究表明 MHb 调节尼古丁厌恶和戒断。然而，尚不清楚 MHb 功能是否仅限于尼古丁和厌恶刺激，或者 MHb 回路是否调节对其他滥用药物的反应。电路级操作的进步现在允许在行为过程中进行细胞类型和时间上的特定操作，特别是在空间限制性的大脑区域，例如 MHb。在这项研究中，我们重点关注 MHb 对可卡因相关行为恢复的反应，证明可卡因引发的条件性位置偏好恢复涉及缰核回路。使用化学遗传学，我们证明 MHb 活性足以诱导恢复行为。总之，这些数据将 MHb 确定为恢复基础电路中的关键枢纽，并可能作为调节类似复发行为的目标。
Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse‐like behaviors are known to be induced, in part, by re‐exposure to drug‐associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse have been identified and studied, a full description of the networks driving reinstatement of drug‐seeking behaviors is lacking. One area that may provide further insight to the mechanisms of relapse is the habenula complex, an epithalamic region composed of lateral and medial (MHb) substructures, each with unique cell and target populations. Although well conserved across vertebrate species, the functions of the MHb are not well understood. Recent research has demonstrated that the MHb regulates nicotine aversion and withdrawal. However, it remains undetermined whether MHb function is limited to nicotine and aversive stimuli or if MHb circuit regulates responses to other drugs of abuse. Advances in circuit‐level manipulations now allow for cell‐type and temporally specific manipulations during behavior, specifically in spatially restrictive brain regions, such as the MHb. In this study, we focus on the response of the MHb to reinstatement of cocaine‐associated behavior, demonstrating that cocaine‐primed reinstatement of conditioned place preference engages habenula circuitry. Using chemogenetics, we demonstrate that MHb activity is sufficient to induce reinstatement behavior. Together, these data identify the MHb as a key hub in the circuitry underlying reinstatement and may serve as a target for regulating relapse‐like behaviors.
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影响因子：
5.3
作者：
Lopez, Alberto J.;Kramar, Enikoe;Wood, Marcelo A.
通讯作者：
Wood, Marcelo A.
影响因子：
5.3
作者：
Augur, Isabel F.;Wyckoff, Andrew R.;Peters, Jamie
通讯作者：
Peters, Jamie
影响因子：
5.8
作者：
Khroyan TV;Yasuda D;Toll L;Polgar WE;Zaveri NT
通讯作者：
Zaveri NT
影响因子：
5.3
作者：
Ji, Huifang;Shepard, Paul D.
通讯作者：
Shepard, Paul D.
DOI：
10.1073/pnas.0906593106
发表时间：
2009-11-10
影响因子：
11.1
作者：
Guettier, Jean-Marc;Gautam, Dinesh;Wess, Juergen
通讯作者：
Wess, Juergen