Nucleus Accumbens and Posterior Amygdala Mediate Cue-Triggered Alcohol Seeking and Suppress Behavior During the Omission of Alcohol-Predictive Cues
Nucleus Accumbens and Posterior Amygdala Mediate Cue-Triggered Alcohol Seeking and Suppress Behavior During the Omission of Alcohol-Predictive Cues
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DOI：
10.1038/npp.2015.102
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发表时间：
2015-10-01
影响因子：
7.6
通讯作者：
Janak, Patricia H.
中科院分区：
文献类型：
--
作者：
Millan, E. Zayra;Reese, Rebecca M.;Janak, Patricia H.
在酒精相关刺激存在的情况下影响行为的神经生物学机制涉及在这些线索存在时组织行为的过程，以及在没有这些线索时对行为的调节。然而，人们对可能调节这一调控的解剖结构知之甚少。在这里，我们研究了伏隔核外壳(AcbSh)作为一种可能的神经底物，介导由酒精相关环境线索和背景的存在和不存在而触发的行为调节。我们还研究了杏仁核基底核的亚区--嘴侧基底外侧核(BLA)和基底后部核(BAP)--因为它们为AcbSh提供了谷氨酸能输入的主要来源。动物被训练在辨别语境中将听觉条件刺激与酒精联系起来，然后在之前与酒精相关或不相关的语境中测试条件性端口进入。我们发现，仅在酒精线索的测试中，AcbSh失活阻止了与酒精相关或新的上下文中的条件端口进入，同时也增加了试验间隔期间的非条件端口进入。当测试酒精强化的线索时，AcbSh失活会产生更多的线索试验遗漏，并增加无条件端口进入。有趣的是，BLA和BAP的失活会产生解离效应。BAP而不是BLA增加了无条件端口进入，而两种操作都阻止了酒精提示期间的条件端口进入。我们得出结论，AcbSh对于调节对行为的控制是必要的，否则就会受到预测酒精的环境刺激和背景的存在的指导。此外，这种作用可能涉及整合杏仁基底核吻部和后部的功能分离的输入。
Neurobiological mechanisms that influence behavior in the presence of alcohol-associated stimuli involve processes that organize behavior during the presence of these cues, and separately, regulation of behavior in their absence. However, little is known about anatomical structures that might mediate this regulation. Here we examined nucleus accumbens shell (AcbSh) as a possible neural substrate mediating behavior modulation triggered by the presence and absence of alcohol-associated environmental cues and contexts. We also examined subregions of basal amygdala nuclei-rostral basolateral (BLA) and basal posterior (BAP)-as they provide a major source of glutamatergic input to the AcbSh. Animals were trained to associate an auditory conditioning stimulus with alcohol in a discriminative context and then subsequently tested for conditioned port-entries across contexts either previously associated or not associated with alcohol. We found that, on test to the alcohol cue alone, AcbSh inactivation prevented conditioned port-entries in contexts that either were associated with alcohol or were novel, while also increasing unconditioned port-entries during the intertrial intervals. When tested to alcohol-reinforced cues, AcbSh inactivation produced more cue-trial omissions and elevated unconditioned port-entries. Interestingly, BLA and BAP inactivation produced dissociable effects. BAP but not BLA increased unconditioned port-entries, while both manipulations prevented conditioned port-entries during the alcohol-cue. We conclude that AcbSh is necessary for modulating control over behavior otherwise guided by the presence of alcohol-predictive environmental stimuli and contexts. Moreover, this role may involve integration of functionally segregated inputs from rostral and posterior portions of basal amygdala nuclei.