BACKGROUND Results from neuroimaging studies suggest that disruptions in flexible decision-making functions in substance-dependent individuals are a consequence of drug-induced neural adaptations. In addicted populations, however, the causal relationship between biobehavioral phenotypes of susceptibility and addiction consequence is difficult to dissociate. Indeed, evidence from animals suggests that poor decision making due to preexisting biological factors can independently enhance the risk for developing addiction-like behaviors. Neuroimaging studies in animals provide a unique translational approach for the identification of the neurobiological mechanisms that mediate susceptibility to addiction. METHODS We used positron emission tomography in rats to quantify regional dopamine D2/3 receptors and metabotropic glutamate receptor 5 (mGluR5) and assessed decision making using a probabilistic reversal learning task. Susceptibility to self-administer cocaine was then quantified for 21 days followed by tests of motivation and relapse-like behaviors. RESULTS We found that deficits specifically in reward-guided choice behavior on the probabilistic reversal learning task predicted greater escalation of cocaine self-administration behavior and greater motivation for cocaine and, critically, were associated with higher midbrain D3 receptor availability. Additionally, individual differences in midbrain D3 receptor availability independently predicted the rate of escalation in cocaine-taking behaviors. No differences in mGluR5 availability, responses during tests of extinction, or cue-induced reinstatement were observed between the groups. CONCLUSIONS These findings indicate that our identified D3-mediated decision-making phenotype can be used as a behavioral biomarker for assessment of cocaine use susceptibility in human populations.

中文翻译：

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中脑 D3 受体可用性预测可卡因自我给药的升级

背景 神经影像学研究的结果表明，物质依赖个体灵活决策功能的中断是药物诱导的神经适应的结果。然而，在成瘾人群中，易感性的生物行为表型与成瘾后果之间的因果关系很难分离。事实上，来自动物的证据表明，由于先前存在的生物因素而导致的糟糕决策可以独立地增加发展成瘾行为的风险。动物的神经影像学研究为鉴定介导成瘾易感性的神经生物学机制提供了一种独特的转化方法。方法 我们在大鼠中使用正电子发射断层扫描来量化局部多巴胺 D2/3 受体和代谢型谷氨酸受体 5 (mGluR5)，并使用概率逆转学习任务评估决策。然后量化自我管理可卡因的敏感性 21 天，然后测试动机和复发样行为。结果我们发现，在概率逆转学习任务中，特别是奖励引导的选择行为的缺陷预示着可卡因自我给药行为的更大升级和更大的可卡因动机，并且至关重要的是，与更高的中脑 D3 受体可用性相关。此外，中脑 D3 受体可用性的个体差异独立地预测了可卡因吸食行为的升级速度。mGluR5 可用性没有差异，在各组之间观察到消退测试或提示诱导的恢复期间的反应。结论 这些研究结果表明，我们确定的 D3 介导的决策表型可用作评估人群中可卡因使用敏感性的行为生物标志物。