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.

中文翻译：

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外侧眶额皮层失活对雄性朗-埃文斯大鼠酒精寻求恢复的选择性影响。

眶额皮质（OFC）在动机行为和决策中发挥着重要作用。在人类中，吸毒者和依赖者（包括那些表现出长期饮酒和酗酒的人）的 OFC 结构和功能受到显着破坏。在动物模型中，OFC 已被证明可以显着影响对非酒精药物滥用的寻求。然而，OFC 在寻求和使用酒精期间的直接调查更为有限。在此报告的研究中，我们在大鼠寻求酒精的多个阶段灭活了外侧（lOFC）或内侧 OFC（mOFC）亚区域。在间歇性使用笼中20%乙醇(EtOH)一个月后，训练大鼠根据FR3时间表自行施用EtOH，并植入针对lOFC或mOFC的插管。我们在乙醇自我给药、灭绝、线索诱导恢复和渐进比例测试过程中用巴氯芬/蝇蕈醇灭活了 OFC 子区域，以广泛表征这些子区域对酒精寻求的影响。在FR3自我给药、消退或渐进比率自我给药期间，mOFC或lOFC失活没有显着影响。然而，lOFC（而不是mOFC）失活显着降低了线索诱导的EtOH寻找恢复。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，支持了先前调查 OFC 在寻求和消费酒精和其他滥用药物中的作用的研究，并表明了 lOFC 与 mOFC 在恢复中的具体作用。