Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR, 97239, USA.
Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR, 97239, USA.
Neuropharmacology. 2022 Feb 1;203:108874. doi: 10.1016/j.neuropharm.2021.108874. Epub 2021 Nov 5.
The nucleus accumbens (NAc) is important for regulating a number of behaviors, including alcohol and substance use. We previously found that chemogenetically manipulating neuronal activity in the NAc core regulates binge-like drinking in mice. The central amygdala (CeA) is also an important regulator of alcohol drinking, and projects to the NAc core. We tested whether neuronal projections from the CeA to the NAc core, or neuropeptides released by the CeA in the NAc core, could regulate binge drinking.
For experiment 1, mice were administered AAV2 Cre-GFP into the NAc core and a Cre-inducible DREADD [AAV2 DIO- hM3Dq, -hM4Di, or -mCherry control] into the CeA. We tested the effects of altering CeA to NAc core activity on binge-like ethanol intake (via "Drinking in the Dark", DID). For experiment 2, we bilaterally microinfused corticotropin releasing factor (CRF), neuropeptide Y (NPY), or somatostatin (SST) into the NAc core prior to DID. For experiment 3, we tested whether intra-NAc CRF antagonism prevented reductions in drinking induced by CNO/hM3Dq stimulation of CeA->NAc projections.
Chemogenetically increasing activity in neurons projecting from the CeA to NAc core decreased binge-like ethanol drinking (p < 0.01). Intra-NAc core CRF mimicked chemogenetic stimulation of this pathway (p < 0.05). Binge-like drinking was unaffected by the doses of NPY and SST tested. Lastly, we found that intra-NAc CRF antagonism prevented reductions in drinking induced by chemogenetic stimulation of CeA->NAc projections. These findings demonstrate that neurons projecting from the CeA to NAc core that release CRF are capable of regulating binge-like drinking in mice.
伏隔核（NAc）在调节多种行为方面很重要，包括酒精和物质的使用。我们之前发现，化学遗传操纵 NAc 核心中的神经元活动可以调节小鼠的 binge-like 饮酒。中央杏仁核（CeA）也是调节饮酒的重要调节剂，并且投射到 NAc 核心。我们测试了 CeA 到 NAc 核心的神经元投射，或者 CeA 中释放到 NAc 核心的神经肽，是否可以调节 binge 饮酒。
对于实验 1，将 AAV2 Cre-GFP 注入 NAc 核心，将 Cre 诱导的 DREADD [AAV2 DIO-hM3Dq、-hM4Di 或-mCherry 对照]注入 CeA。我们测试了改变 CeA 到 NAc 核心活动对 binge-like 乙醇摄入的影响（通过“在黑暗中饮酒”，DID）。对于实验 2，我们在 DID 之前双侧微注射促肾上腺皮质激素释放因子（CRF）、神经肽 Y（NPY）或生长抑素（SST）到 NAc 核心。对于实验 3，我们测试了 NAc 内 CRF 拮抗是否可以防止 CNO/hM3Dq 刺激 CeA->NAc 投射引起的饮酒减少。
化学遗传地增加从 CeA 投射到 NAc 核心的神经元活动会减少 binge-like 乙醇摄入（p < 0.01）。NAc 内 CRF 模拟了该途径的化学遗传刺激（p < 0.05）。测试的 NPY 和 SST 剂量对 binge-like 饮酒没有影响。最后，我们发现 NAc 内 CRF 拮抗可以防止化学遗传刺激 CeA->NAc 投射引起的饮酒减少。这些发现表明，从 CeA 投射到 NAc 核心并释放 CRF 的神经元能够调节小鼠的 binge-like 饮酒。
