BACKGROUND Individuals addicted to cocaine spend much of their time foraging for the drug. Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use. The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala (BLA) and the nucleus accumbens core (NAcC). However, the precise neuronal circuits underlying the acquisition of cue-controlled cocaine-seeking behavior have not been elucidated. METHODS Here, we used a projection-specific Cre-dependent DREADD (designer receptor exclusively activated by designer drugs)-mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine-seeking behavior. RESULTS In Sprague Dawley rats with Cre-mediated expression of the inhibitory DREADD hM4D(Gi) in the NAcC-projecting BLA neurons, treatment with clozapine N-oxide, but not vehicle, selectively prevented the impact of cocaine-associated conditioned reinforcers on cocaine seeking under a second-order schedule of reinforcement. This effect was attributable to the chemogenetic inhibition of the NAcC-projecting BLA neurons, as it was reversible, and it was absent in clozapine N-oxide-treated rats expressing an empty control virus. In contrast, chemogenetic inhibition of the anterior insula, which receives collateral projections from NAcC-projecting BLA neurons, was without effect. CONCLUSIONS These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues requires activity in the direct projections from the BLA to the NAcC.

中文翻译：

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基底外侧杏仁核 → 伏隔核核心回路介导可卡因配对线索对可卡因寻求的条件强化作用。

背景对可卡因上瘾的个体花费大量时间来寻找药物。巴甫洛夫药物相关的条件刺激对药物寻求的启动和维持产生重大影响，通常长期禁欲，特别是当出现反应时，作为条件性强化物，将延迟药物使用延迟。获得线索控制的可卡因搜索已被证明取决于基底外侧杏仁核 (BLA) 和伏隔核核心 (NAcC) 之间的功能相互作用。然而，尚未阐明获得线索控制的可卡因寻求行为背后的精确神经元回路。方法在这里，我们使用了投射特定的 Cre 依赖 DREADD（由设计药物专门激活的设计受体）介导的因果方法来测试从 BLA 到 NAcC 的直接投射是获得线索控制的可卡因寻求行为所必需的假设. 结果 在 Sprague Dawley 大鼠中，在 NAcC 投射 BLA 神经元中具有 Cre 介导的抑制性 DREADD hM4D(Gi) 表达，用氯氮平 N-氧化物治疗，而不是载体，选择性地阻止了可卡因相关条件强化剂对可卡因寻求的影响在二阶强化计划下。这种作用归因于 NAcC 投射 BLA 神经元的化学遗传抑制，因为它是可逆的，并且在表达空对照病毒的氯氮平 N-氧化物处理的大鼠中不存在。相比之下，前岛叶的化学遗传学抑制从 NAcC 投射 BLA 神经元接收侧枝投射，但没有效果。结论 这些数据表明，依赖于可卡因线索的条件强化效应的线索控制的可卡因寻求的获取需要从 BLA 到 NAcC 的直接投射中的活动。