Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences.
Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences.
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DOI：
10.3390/ijms22116113
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发表时间：
2021-06-06
影响因子：
5.6
通讯作者：
Knackstedt LA
中科院分区：
文献类型：
--
作者：
Schwendt M;Knackstedt LA
静脉注射可卡因自我给药模型被广泛用于表征可卡因寻求的神经生物学。当研究的目的是了解可卡因的复发情况时，会实施可卡因戒断期，然后进行“复发”测试，以评估药物相关刺激（“启动”）引起先前为获取可卡因而做出的工具反应的恢复的能力。在这里，我们回顾了关于可卡因戒断程序对神经生物学影响的文献，发现前额叶皮层的前边缘和下边缘区域是通过消退训练而招募的，当不进行消退训练时，它们不是复发回路的一部分。将可卡因输注与离散线索配对会招募 NA 的参与，无论戒断程序如何，NA 与背侧纹状体一起都是复发回路的关键部分。 NA 核心分子适应的差异包括消退训练后 GluN1 和谷氨酸受体信号传导伙伴的表达增加。 AMPA 受体和谷氨酸转运蛋白同样受到禁欲和消退的影响。谷氨酸受体拮抗剂显示出在减少消退和戒断后复发方面的功效，并且在消退训练后恢复谷氨酸稳态的化合物的功效略有增加。人类成像研究揭示了可卡因引起的适应与灭绝训练后产生的适应相似。因此，虽然工具性消退训练不具有表面有效性，但其使用不会产生与人类可卡因使用者不同的适应。
The intravenous cocaine self-administration model is widely used to characterize the neurobiology of cocaine seeking. When studies are aimed at understanding relapse to cocaine-seeking, a post-cocaine abstinence period is imposed, followed by “relapse” tests to assess the ability of drug-related stimuli (“primes”) to evoke the resumption of the instrumental response previously made to obtain cocaine. Here, we review the literature on the impact of post-cocaine abstinence procedures on neurobiology, finding that the prelimbic and infralimbic regions of the prefrontal cortex are recruited by extinction training, and are not part of the relapse circuitry when extinction training does not occur. Pairing cocaine infusions with discrete cues recruits the involvement of the NA, which together with the dorsal striatum, is a key part of the relapse circuit regardless of abstinence procedures. Differences in molecular adaptations in the NA core include increased expression of GluN1 and glutamate receptor signaling partners after extinction training. AMPA receptors and glutamate transporters are similarly affected by abstinence and extinction. Glutamate receptor antagonists show efficacy at reducing relapse following extinction and abstinence, with a modest increase in efficacy of compounds that restore glutamate homeostasis after extinction training. Imaging studies in humans reveal cocaine-induced adaptations that are similar to those produced after extinction training. Thus, while instrumental extinction training does not have face validity, its use does not produce adaptations distinct from human cocaine users.
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