Suppr超能文献

强迫应对行为的发展依赖于背外侧纹状体多巴胺依赖的机制。

The development of compulsive coping behavior depends on dorsolateral striatum dopamine-dependent mechanisms.

机构信息

Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.

Astra Zeneca, R&D Biopharmaceuticals, Fleming Building (B623), Babraham Research Park, Babraham, Cambridgeshire, CB22 3AT, UK.

出版信息

Mol Psychiatry. 2023 Nov;28(11):4666-4678. doi: 10.1038/s41380-023-02256-z. Epub 2023 Sep 28.

Abstract

Humans greatly differ in how they cope with stress, a natural behavior learnt through negative reinforcement. Some individuals engage in displacement activities, others in exercise or comfort eating, and others still in alcohol use. Across species, adjunctive behaviors, such as polydipsic drinking, are used as a form of displacement activity that reduces stress. Some individuals, in particular those that use alcohol to self-medicate, tend to lose control over such coping behaviors, which become excessive and compulsive. However, the psychological and neural mechanisms underlying this individual vulnerability have not been elucidated. Here we tested the hypothesis that the development of compulsive adjunctive behaviors stems from the functional engagement of the dorsolateral striatum (DLS) dopamine-dependent habit system after a prolonged history of adjunctive responding. We measured in longitudinal studies in male Sprague Dawley rats the sensitivity of early established vs compulsive polydipsic water or alcohol drinking to a bilateral infusion into the anterior DLS (aDLS) of the dopamine receptor antagonist α-flupentixol. While most rats acquired a polydipsic drinking response with water, others only did so with alcohol. Whether drinking water or alcohol, the acquisition of this coping response was insensitive to aDLS dopamine receptor blockade. In contrast, after prolonged experience, adjunctive drinking became dependent on aDLS dopamine at a time when it was compulsive in vulnerable individuals. These data suggest that habits may develop out of negative reinforcement and that the engagement of their underlying striatal system is necessary for the manifestation of compulsive adjunctive behaviors.

摘要

人类在应对压力方面有很大的差异,这是一种通过负强化习得的自然行为。一些人会从事替代活动,另一些人则会运动或舒适地进食,还有一些人则会饮酒。在不同物种中,辅助行为,如多饮,被用作减轻压力的替代活动形式。一些人,特别是那些用酒精自我治疗的人,往往会失去对这些应对行为的控制,这些行为变得过度和强迫。然而,这种个体脆弱性的心理和神经机制尚未阐明。在这里,我们测试了这样一个假设,即强迫性辅助行为的发展源于背外侧纹状体(DLS)多巴胺依赖习惯系统的功能参与,在长期的辅助反应后。我们在雄性 Sprague Dawley 大鼠的纵向研究中测量了早期建立的与强迫性多饮性水或酒精摄入的敏感性,以评估双侧前背外侧纹状体(aDLS)多巴胺受体拮抗剂α-氟哌啶醇的影响。虽然大多数大鼠通过饮水获得了多饮性饮水反应,但其他大鼠仅通过饮酒获得。无论是饮水还是饮酒,这种应对反应的获得对 aDLS 多巴胺受体阻断均不敏感。相比之下,在长期的经验之后,辅助性饮酒变得依赖于 aDLS 多巴胺,而此时在易感性个体中,它是强迫性的。这些数据表明,习惯可能是从负强化中发展出来的,而其潜在纹状体系统的参与是表现出强迫性辅助行为的必要条件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ac8/10914627/e7e9e30aa789/41380_2023_2256_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验