Anterior Insular Cortex is Critical for the Propensity to Relapse Following Punishment-Imposed Abstinence of Alcohol Seeking
Anterior Insular Cortex is Critical for the Propensity to Relapse Following Punishment-Imposed Abstinence of Alcohol Seeking
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DOI：
10.1523/jneurosci.1596-18.2018
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发表时间：
2019-02-06
影响因子：
5.3
通讯作者：
Lawrence, Andrew J.
中科院分区：
文献类型：
--
作者：
Campbell, Erin J.;Flanagan, Jeremy P. M.;Lawrence, Andrew J.
患有酒精使用障碍的人通常会因为与过度饮酒相关的负面后果而戒酒，并且暴露于先前与酒精使用相关的环境可能会引发复发。我们使用了一个大鼠模型，它捕捉了这种人类状况的一个特征：即由于偶然的惩罚而自愿戒酒。长期戒酒后复发的倾向有很大的差异，这是阻止成功治疗酒精使用障碍的一个关键特征。在这里，我们研究了急性或长期禁欲后复发。在偏好酒精的雄性大鼠中，我们发现在情境B（长期禁欲后的惩罚情境）中复发的倾向增加。接下来，我们发现酒精摄入史和酒精的动机强度都不能预测复发的倾向。接下来，我们使用Fos作为神经元激活的标志物，研究了长期戒酒后情境诱导的酒精寻求复发的假定回路。在情境B中，前岛叶皮层（AI）是唯一一个被检测到Fos表达与长期戒酒后的酒精寻求行为相关的脑区。最后，我们使用GABA（A）和GABA（B）受体激动剂（蝇蕈醇+巴氯芬）的局部输注来显示AI在情境B（长期禁欲后的惩罚情境）中情境诱导的复发中的因果作用。我们的研究结果表明，在惩罚相关的背景下，长期禁欲后，复发的倾向有很大的个体差异，这是由AI的活动介导的。
Humans with alcohol use disorder typically abstain because of the negative consequences associated with excessive drinking, and exposure to contexts previously associated with alcohol use can trigger relapse. We used a rat model that captures a characteristic of this human condition: namely voluntary abstinence from alcohol use because of contingent punishment. There is substantial variability in the propensity to relapse following extended periods of abstinence, and this is a critical feature preventing the successful treatment of alcohol use disorder. Here we examined relapse following acute or prolonged abstinence. In male alcohol preferring P rats, we found an increased propensity to relapse in Context B, the punishment context after prolonged abstinence. Next, we found that neither alcohol intake history nor the motivational strength of alcohol predicted the propensity to relapse. We next examined the putative circuitry of context-induced relapse to alcohol seeking following prolonged abstinence using Fos as a marker of neuronal activation. The anterior insular cortex (AI) was the only brain region examined where Fos expression correlated with alcohol seeking behavior in Context B after prolonged abstinence. Finally, we used local infusion of GABA(A) and GABA(B) receptor agonists(muscimol + baclofen) to showa causal role of the AI in context-induced relapse in Context B, the punishment context after prolonged abstinence. Our results show that there is substantial individual variability in the propensity to relapse in the punishment-associated context after prolonged abstinence, and this is mediated by activity in the AI.