Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States.
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States.
Brain Res. 2023 May 15;1807:148323. doi: 10.1016/j.brainres.2023.148323. Epub 2023 Mar 11.
Identifying neurobiological characteristics that predict the development of cocaine use disorder would be of great value in prevention efforts. Because of their importance in mediating the abuse-related effects of cocaine, brain dopamine receptors are logical candidates for investigation. We analyzed data from two recently published studies that characterized availability of dopamine D2-like receptors (D2R) with [C]raclopride PET imaging and dopamine D receptor (DR) sensitivity with quinpirole-induced yawning in cocaine-naïve rhesus monkeys who subsequently acquired cocaine self-administration and completed a cocaine self-administration dose-effect curve. The present analysis compared D2R availability in several brain areas and characteristics of quinpirole-induced yawning, both acquired when monkeys were drug-naïve, with measures of initial sensitivity to cocaine. D2R availability in the caudate nucleus was negatively correlated with the ED of the cocaine self-administration curve, although the significance of this relationship was driven by an outlier and was not present after the outlier was removed. No other significant associations were observed between D2R availability in any examined brain region and measures of sensitivity to cocaine reinforcement. However, there was a significant negative correlation between DR sensitivity, represented by the ED of the quinpirole-induced yawning curve, and the dose at which monkeys acquired cocaine self-administration. We also report no change from baseline D2R availability when a second PET scan was conducted after completion of the dose-effect curves. These data suggest the utility of DR sensitivity, but not D2R availability, as a biomarker for vulnerability and resilience to cocaine. The well-established relationships between dopamine receptors and cocaine reinforcement in cocaine-experienced humans and animals may require extensive cocaine exposure.
确定可预测可卡因使用障碍发展的神经生物学特征对于预防工作将具有重要价值。由于脑多巴胺受体在介导可卡因的滥用相关效应方面具有重要作用，因此它们是研究的合理候选者。我们分析了两项最近发表的研究的数据，这些研究使用 [C]raclopride PET 成像来描述多巴胺 D2 样受体（D2R）的可用性，并使用喹吡罗诱导哈欠来描述多巴胺 D 受体（DR）敏感性，这些研究对象是随后获得可卡因自我给药并完成可卡因自我给药剂量-效应曲线的可卡因-naïve 恒河猴。本分析比较了猴子在药物-naïve 时获得的几个脑区中的 D2R 可用性和喹吡罗诱导哈欠的特征，以及对可卡因初始敏感性的测量。尾状核中的 D2R 可用性与可卡因自我给药曲线的 ED 呈负相关，尽管这种关系的显著性是由一个异常值驱动的，并且在去除异常值后并不存在。在任何检查的脑区中，D2R 可用性与可卡因强化敏感性的测量之间均未观察到其他显著相关性。然而，DR 敏感性（由喹吡罗诱导哈欠曲线的 ED 表示）与猴子获得可卡因自我给药的剂量之间存在显著负相关。我们还报告说，在完成剂量-效应曲线后进行第二次 PET 扫描时，基线 D2R 可用性没有变化。这些数据表明，DR 敏感性而非 D2R 可用性可用作易感性和对可卡因的弹性的生物标志物。在可卡因经验丰富的人类和动物中，多巴胺受体与可卡因强化之间的既定关系可能需要广泛的可卡因暴露。
