Inactivation of the lateral habenula reduces anxiogenic behavior and cocaine seeking under conditions of heightened stress.
Inactivation of the lateral habenula reduces anxiogenic behavior and cocaine seeking under conditions of heightened stress.
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DOI：
10.1016/j.pbb.2013.08.002
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发表时间：
2013-10
影响因子：
3.6
通讯作者：
See, Ronald E.
中科院分区：
文献类型：
--
作者：
Gill, Margaret J.;Ghee, Shannon M.;Harper, Stiles M.;See, Ronald E.
最近的解剖学和功能研究重新引起了人们对外侧缰（LHb）的兴趣，这是一个关键的大脑区域，以对抗的方式调节厌恶和食欲过程。特别地，增加的LHb激活被认为在应激条件下驱动焦虑状态。在这里，我们可逆地失活的LHb与GABA受体激动剂（巴氯芬/蝇蕈醇）在大鼠在一个开放的领域，高架十字迷宫和防御性埋葬任务在育亨宾，去甲肾上腺素能α2受体拮抗剂，作为一种焦虑应激的存在或不存在的测试之前。在第二组实验中，使用可卡因自我管理和恢复模型，我们灭活的LHb在灭绝响应和线索诱导恢复可卡因寻求在存在或不存在育亨宾预处理。育亨宾治疗后LHb的失活通过增加张开双臂的时间和减少掩埋的时间来减弱焦虑行为。失活的LHb也减少可卡因寻求线索诱导的恢复发生在育亨宾的存在下，但不影响灭绝反应或线索诱导的恢复本身。这些数据表明，LHb在无条件行为和有条件食欲过程中严格调节高度焦虑状态。
Recent anatomical and functional studies have renewed interest in the lateral habenula (LHb), a critical brain region that works in an opponent manner to modulate aversive and appetitive processes. In particular, increased LHb activation is believed to drive anxiogenic states during stressful conditions. Here, we reversibly inactivated the LHb with GABA receptor agonists (baclofen/muscimol) in rats prior to testing in an open field, elevated plus maze, and defensive burying task in the presence or absence of yohimbine, a noradrenergic α2-receptor antagonist that acts as an anxiogenic stressor. In a second set of experiments using a cocaine self-administration and reinstatement model, we inactivated the LHb during extinction responding and cue-induced reinstatement of cocaine seeking in the presence or absence of yohimbine pretreatment. Inactivation of the LHb after yohimbine treatment attenuated anxiogenic behavior by increasing time spent in the open arms and reducing the time spent burying. Inactivation of the LHb also reduced cocaine seeking when cue-induced reinstatement occurred in the presence of yohimbine, but did not affect extinction responding or cue-induced reinstatement by itself. These data demonstrate that the LHb critically regulates states of heightened anxiety during both unconditioned behavior and conditioned appetitive processes.
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影响因子：
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