Selective impact of lateral orbitofrontal cortex inactivation on reinstatement of alcohol seeking in male Long-Evans rats.
Selective impact of lateral orbitofrontal cortex inactivation on reinstatement of alcohol seeking in male Long-Evans rats.
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DOI：
10.1016/j.neuropharm.2020.108007
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发表时间：
2020-05-15
影响因子：
4.7
通讯作者：
Moorman, David E.
中科院分区：
文献类型：
--
作者：
Arinze, Ifeyinwa;Moorman, David E.
眶额皮质（OFC）在动机行为和决策中起着重要作用。在人类中，药物使用和依赖个体，包括那些表现出慢性酒精使用和酒精中毒的个体，OFC结构和功能显着破坏。在动物模型中，OFC已被证明对寻求非酒精药物滥用有显著影响。然而，在寻求和使用酒精期间对OFC的直接调查更为有限。在本文报道的研究中，我们在大鼠的多个酒精寻求阶段灭活了外侧（lOFC）或内侧OFC （mOFC）亚区。在一个月的间歇使用20%乙醇（EtOH）后，大鼠被训练成在FR3计划下自行使用EtOH，并植入指向lOFC或mOFC的套管。我们在EtOH自我给药、消失、线索诱导恢复和渐进式比率测试中使用巴氯芬/muscimol灭活OFC亚区，以广泛表征这些亚区对酒精寻求的影响。在FR3自我给药、消失或递进比例自我给药期间，mOFC或lOFC失活没有显著影响。然而，lOFC而非mOFC的失活显著降低了线索诱导的EtOH寻求恢复。这些发现为OFC操纵对操作性酒精寻求的具体影响提供了新的信息，支持了之前关于OFC在酒精和其他滥用药物的寻求和消费中的作用的研究，并表明lOFC与mOFC在恢复中的特定作用。
The orbitofrontal cortex (OFC) plays a fundamental role in motivated behavior and decision-making. In humans, OFC structure and function is significantly disrupted in drug using and dependent individuals, including those exhibiting chronic alcohol use and alcoholism. In animal models, the OFC has been shown to significantly influence the seeking of non-alcohol drugs of abuse. However direct investigations of the OFC during alcohol seeking and use have been more limited. In the studies reported here, we inactivated lateral (lOFC) or medial OFC (mOFC) subregions in rats during multiple stages of alcohol seeking. After one month of intermittent access to homecage 20% ethanol (EtOH), rats were trained to self-administer EtOH under an FR3 schedule and implanted with cannulae directed to lOFC or mOFC. We inactivated OFC subregions with baclofen/muscimol during EtOH self-administration, extinction, cue-induced reinstatement, and progressive ratio testing to broadly characterize the influence of these subregions on alcohol seeking. There were no significant effects of mOFC or lOFC inactivation during FR3 self-administration, extinction, or progressive ratio self-administration. However, lOFC, and not mOFC, inactivation significantly decreased cue-induced reinstatement of EtOH seeking. These findings contribute new information to the specific impact of OFC manipulation on operant alcohol seeking, support previous studies investigating the role of OFC in seeking and consumption of alcohol and other drugs of abuse, and indicate a specific role for lOFC vs. mOFC in reinstatement.
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影响因子：
3.7
作者：
Clark, Jeremy J.;Nasrallah, Nicholas A.;Phillips, Paul E. M.
通讯作者：
Phillips, Paul E. M.
影响因子：
3.6
作者：
Boettiger, Charlotte A.;Kelley, Elizabeth A.;Mitchell, Jennifer M.;D'Esposito, Mark;Fields, Howard L.
通讯作者：
Fields, Howard L.
侧眶额皮质的失活会增加乙醇依赖性但非依赖性小鼠的饮用。
影响因子：
4.7
作者：
den Hartog C;Zamudio-Bulcock P;Nimitvilai S;Gilstrap M;Eaton B;Fedarovich H;Motts A;Woodward JJ
通讯作者：
Woodward JJ
影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
影响因子：
7.6
作者：
Arguello, Amy A.;Richardson, Ben D.;Fuchs, Rita A.
通讯作者：
Fuchs, Rita A.