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个体间冲动/强迫维度的差异:在静息状态下破译相关的多巴胺能和血清素能代谢。

Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.

机构信息

INCIA, UMR 5287, Univ. Bordeaux, F-33000 Bordeaux, France

INCIA, UMR 5287, CNRS, F-33000 Bordeaux, France.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2018 Apr 19;373(1744). doi: 10.1098/rstb.2017.0154.

Abstract

Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

摘要

几种冲动控制障碍,如 ADHD、躁狂症、人格障碍或物质滥用,具有共同的行为特征,如冲动、冒险或行为僵化。这些疾病的治疗方法是使用针对多巴胺(DA)和/或 5-羟色胺(5-HT)的药物。然而,这些神经递质补偿的患者单胺失衡尚不清楚。本研究旨在调查与冲动性/强迫性的六个主要成分(预期多动、过早反应、延迟折扣、冒险、坚持、灵活性)的个体间变异性相关的选定大脑区域内的 DA 和 5-HT 代谢在静息状态下的模式。在每个任务中都确定了具有适应性和高度不适应性行为的大鼠,并且敏感的生化方法允许在 20 个大脑区域中映射死后内源性单胺组织含量。根据行为特征揭示了 5-HT 和 DA 代谢的不同模式。除了多动反应外,动作控制能力较低主要与前额叶和/或皮质下区域(即眶额皮质(DA)、杏仁核和前扣带皮质(5-HT))的较低 DA 或 5-HT 代谢相关,对不灵活和冒险的大鼠)。我们的研究结果通过与冲动控制障碍相关的单胺能网络,揭示了与冲动控制障碍相关的行为特征的复杂性,为理解精神障碍和药物治疗作用之间的联系铺平了道路。本文是主题为“多样性的不同视角:个体差异的多学科方法”的一部分。

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