Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Neuroscience Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Neuropharmacology. 2018 Mar 1;130:42-53. doi: 10.1016/j.neuropharm.2017.11.035. Epub 2017 Nov 26.
The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4D-Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC→AcbC or IC→AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC→AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC→AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration.
皮质纹状体脑回路在药物使用中起着重要作用。因此，本研究调查了皮质纹状体回路在调节酒精自我给药中的功能作用。鉴于已经确定了伏隔核核心（AcbC）在调节酒精强化反应中的功能作用，我们试图测试皮质脑区在调节酒精自我给药中的作用，这些皮质脑区与 AcbC 有传入投射：前额叶皮质（mPFC）和岛叶皮质（IC）。长爪沙鼠被训练在 30 分钟的时间内自行摄取酒精（15%酒精（v/v）+2%蔗糖（w/v））。为了测试 mPFC 或 IC 的功能作用，我们使用化学遗传技术（hM4D-Designer Receptors Activation by Designer Drugs）在酒精自我给药之前沉默神经元活动。此外，我们化学遗传沉默 mPFC→AcbC 或 IC→AcbC 投射，以研究皮质纹状体回路在调节酒精自我给药中的作用。化学遗传沉默 mPFC 减少了酒精自我给药，而沉默 IC 增加了酒精自我给药，而 mCherry-Controls 中则没有这种作用。有趣的是，沉默 mPFC→AcbC 投射对酒精自我给药没有影响。相比之下，沉默 IC→AcbC 投射以强化物特异性的方式减少了酒精自我给药，而在训练大鼠自行摄取蔗糖（0.8%，w/v）的情况下则没有影响。此外，在 mCherry-Controls 中也没有观察到自我给药的变化。这些数据共同表明了皮质纹状体回路的复杂作用，同时暗示了岛叶纹状体回路在调节持续的酒精自我给药中的作用。
