Comparative neuropsychopharmacology of methamphetamine (“Crystal Meth”) and MDMA (“Ecstasy”) on facets of cognitive control and impulsive behavior in social and non-social contexts: integrating behavior, psychophysiology, and neurochemistry

甲基苯丙胺（“水晶甲基”）和摇头丸（“摇头丸”）在社交和非社交环境中认知控制和冲动行为方面的比较神经精神药理学：整合行为、心理生理学和神经化学

• 批准号: 400563219
• 负责人: Professor Dr. Christian Beste
• 金额: --
• 依托单位: Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/400563219?language=en
• 关键词: Comparative; neuropsychopharmacology; methamphetamine; Crystal; Meth

The use of methamphetamine (METH, “Crystal Meth”) and 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) currently increases in Europe. Previous work has shown that both METH and MDMA users suffer from overlapping but also different deficits in a variety of impulse control functions that are related to the specific chronic effects of the drugs on monoamine, glutamate, and gamma-aminobutyric acid (GABA) systems. In particular, cognitive impairments impact the social functions of the users. The main goal of this project is to compare the chronic effects of METH and MDMA on the modulation of different facets of impulsive behavior by social and non-social contexts, as well as on the underlying functional brain mechanisms. These comparisons are achieved by employing a multi-method approach integrating behavioral and electrophysiological (EEG) data with neurochemical information derived from magnetic resonance spectroscopy (MRS). We investigate the effect of varying emotional contents (such as angriness and happiness) during conflict monitoring processes requiring inhibitory control mechanisms. In a second experimental paradigm we examine premature responding impulsivity (PRI) during contexts of reward acquisition and loss avoidance using computational modelling. We relate psychophysiological processes underlying modulations of different facets of impulsive behavior by social and non-social contexts to structural-neurobiochemical changes at the striatal GABA and GLU level in METH and MDMA users. This allows a comprehensive evaluation and comparison of mechanistic factors at a structure-specific neurochemical level with neurophysiology and behavior. The focus on the GABAergic and glutamatergic changes in the basal ganglia is important, given that compounds modulating these systems may be interesting candidates in the treatment of stimulant addiction. Thus, the project is crucial to discover new therapeutic approaches in order to i) improve impulse control deficits and related social problems in the daily life of the METH and MDMA users and ii) to better treat METH addiction for which no approved pharmacological treatment exists so far.

甲基苯丙胺（METH，“Crystal Meth”）和3，4-亚甲二氧基甲基苯丙胺（MDMA，“Ecastrazine”）的使用目前在欧洲有所增加。先前的研究表明，METH和MDMA使用者在各种冲动控制功能方面存在重叠但不同的缺陷，这些功能与药物对单胺，谷氨酸和γ-氨基丁酸（GABA）系统的特定慢性效应有关。特别是，认知障碍影响用户的社会功能。该项目的主要目标是比较METH和MDMA对社会和非社会背景下冲动行为不同方面的调制以及对潜在功能性大脑机制的慢性影响。这些比较是通过采用多方法的方法整合行为和电生理（EEG）数据与来自磁共振波谱（MRS）的神经化学信息。我们调查的影响，不同的情绪内容（如愤怒和幸福）在冲突监测过程中需要抑制控制机制。在第二个实验范例中，我们研究过早的反应冲动（PRI）的背景下，奖励收购和损失避免使用计算建模。我们涉及的心理生理过程的调制的不同方面的冲动行为的社会和非社会背景的结构神经生化变化在纹状体的GABA和GLU水平的甲基和摇头丸用户。这允许在结构特异性神经化学水平上与神经生理学和行为学对机械因素进行全面评估和比较。对基底神经节中GABA能和多巴胺能变化的关注是重要的，因为调节这些系统的化合物可能是治疗兴奋剂成瘾的有趣候选物。因此，该项目对于发现新的治疗方法至关重要，以便i）改善METH和MDMA使用者日常生活中的冲动控制缺陷和相关社会问题，ii）更好地治疗迄今为止尚未批准的药物治疗的METH成瘾。