Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.
Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.
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DOI：
10.1371/journal.pone.0092701
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Taha SA
中科院分区：
文献类型：
--
作者：
Haack AK;Sheth C;Schwager AL;Sinclair MS;Tandon S;Taha SA
外侧缰核（LHb）在负性结果驱动的学习中起着重要作用。包括乙醇在内的许多滥用药物具有剂量依赖性的厌恶效应，从而限制药物的摄入。然而，LHb在调节乙醇摄入中的作用尚不清楚。在本研究中，我们比较自愿乙醇消费和自我管理，育亨宾诱导恢复乙醇寻求，乙醇诱导的条件性味觉厌恶与假或LHb病变的大鼠。在间歇性进入两瓶选择范式中给予20%乙醇的大鼠中，损伤动物比假损伤对照动物更快地增加其自愿乙醇消耗量，并保持更高的自愿乙醇摄入稳定率。同样，损伤的动物表现出较高的响应率乙醇在操作性自我管理会议。此外，LHb损伤阻断育亨宾诱导的乙醇寻求消退后的恢复。最后，LHb损伤显着减弱乙醇诱导的条件性味觉厌恶。我们的研究结果表明，在多个方面的乙醇导向行为的LHb的重要作用，并进一步表明，LHb可能有助于乙醇导向的行为，通过介导的学习驱动的药物的厌恶效应。
The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.
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影响因子：
3.7
作者：
Matsumoto M;Hikosaka O
通讯作者：
Hikosaka O
影响因子：
3.7
作者：
Brown PL;Shepard PD
通讯作者：
Shepard PD
影响因子：
2.3
作者：
Camicella, Sebastien;Amamoto, Ryoji;Ron, Dorit
通讯作者：
Ron, Dorit
影响因子：
2.9
作者：
DONOVICK, PJ;BURRIGHT, RG;ROSENSTREICH, N
通讯作者：
ROSENSTREICH, N
影响因子：
16.2
作者：
Jhou, Thomas C.;Fields, Howard L.;Baxter, Mark G.;Saper, Clifford B.;Holland, Peter C.
通讯作者：
Holland, Peter C.