Determining the effects of "bath salts" on cognitive control and functional brain connectivity

确定“浴盐”对认知控制和功能性大脑连接的影响

• 批准号: 10376204
• 负责人: Luis M Colon-Perez
• 金额: $ 17.2万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376204
• 关键词: Acute; Address; Adverse effects; Affect; Amygdaloid structure; Attention; Automobile Driving; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; Chronic; Cocaine; Complex; Consumption; Corpus striatum structure; Dangerousness; Data; Dopamine; Drug Use Disorder; Exposure to; Functional Magnetic Resonance Imaging; Genes; Grant; Health Professional; Healthcare; Hour; Impairment; Impulsivity; Information Storage; Intravenous; Knowledge; Lead; Long-Term Effects; Longitudinal Studies; Mediation; Memory; Mental Processes; Messenger RNA; Modeling; Monitor; Motor Activity; Neurons; Neurophysiology - biologic function; Nuclear; Nucleus Accumbens; Outcome; Pattern; Performance; Pharmaceutical Preparations; Pharmacology; Publishing; Rattus; Research; Rest; Rewards; Rodent; Self Administration; Social Interaction; Structure; Substance Use Disorder; Task Performances; Techniques; Testing; Thalamic structure; Time; Training; abuse liability; base; bath salts; behavioral outcome; brain circuitry; career; cognitive change; cognitive control; cognitive function; cognitive testing; cognitive training; design; discounting; drug seeking behavior; environmental change; flexibility; frontal lobe; goal oriented behavior; interest; mRNA Expression; mental set; neuroimaging; neurotransmission; preference; relating to nervous system; response; skills; substance use

Abstract “Bath salts” or synthetic cathinones drugs potential of chronic use, ability to alter behaviors like cognitive control and alterations in the brain makes them a significant healthcare concern. One of the most harmful bath salts is 3,4-methylenedioxypyrovalerone (MDPV). The adverse behavioral effects of MDPV can last days-to- weeks possibly due to alteration in dopamine neurotransmissions. Research into drug has shown that MDPV is similar pharmacologically to cocaine but longer lasting. However, an essential unexplored aspect of MDPV is how it alters cognitive control and whether changed cognitive control underlies some of the most severe behavioral outcomes of MDPV use. Cognitive control refers to a set of mental processes driving the organization and mediation of goal-oriented behavior. In this grant, two specific cognitive control domains of interest are flexibility and impulsivity. These two subprocesses are compromised in substance use disorders and can lead to uncontrolled drug-seeking behavior. Using fMRI, we recently showed that after 24 hours an acute MDPV administration in rats caused an increase in brain connectivity specifically in frontal cortical regions such as orbitofrontal (OrF), infralimbic (IL), prelimbic (PL) and subcortical reward regions including striatum, amygdala, and nucleus accumbens (NAc). These changes in connectivity could underlie some of the most dangerous effects of MDPV by inducing long-lasting changes in the connectivity of cognitive control brain circuitry. Therefore, we hypothesize that sustained self-administration of MDPV will increase functional connectivity between the frontal cortex (PL, IL, and OrF), thalamus, amygdala, and NAc leading to impairments in cognitive control functions. We will test this hypothesis using rodents trained to chronically self-administer MDPV for ten days. The proposed research is designed to address existing gaps in our understanding of how MDPV undermines cognitive control and which brain regions are most affected and calculating connectivity changes in the brain with fMRI. In this project, the candidate will assess two subprocesses of cognitive control, impulsivity, and flexibility. The behavior will be analyzed concerning functional connectivity changes of longitudinal resting state fMRI (rsfMRI) data, and neuronal performance-dependent activity using activity regulated cytoskeletal-associated gene (Arc) mRNA expression in rats. Carrying out the proposed research will permit the candidate to incur in an independent research career integrating longitudinal studies of rsfMRI connectivity, behavioral, and Arc cellular analysis into studies of drug use disorders.

抽象的 “沐浴沙拉”或合成Cathinones药物的慢性使用潜力，更改诸如认知之类的行为的能力 大脑中的控制和改变使它们成为重要的医疗保健问题。最有害的浴室之一 盐为3,4-甲基二甲基二回甲甲甲基（MDPV）。 MDPV的不利行为影响可能持续到天数 几周可能是由于多巴胺神经递送的改变。对药物的研究表明，MDPV是 与可卡因相似，但持久持久。但是，MDPV的一个基本意外方面是 它如何改变认知控制以及改变认知控制是否是一些最严重的基础 MDPV使用的行为结果。认知控制是指推动驱动的一系列心理过程 以目标为导向行为的组织和调解。在这笔赠款中，两个特定的认知控制领域 兴趣是灵活的和冲动的。这两个子过程在物质使用障碍中受到损害 并可能导致不受控制的毒品行为。使用fMRI，我们最近表明24小时后 大鼠的急性MDPV给药导致脑部皮质中的大脑连通性提高 诸如轨道额（ORF），Infralimbic（IL），前比（PL）和皮层下奖励区域等地区 纹状体，杏仁核和伏隔核（NAC）。这些连通性的变化可能是一些 MDPV最危险的效果通过引起认知控制大脑连通性的持久变化 电路。因此，我们假设MDPV的持续自我管理将增加功能 额叶皮层（PL，IL和ORF），丘脑，杏仁核和NAC之间的连通性导致损害 在认知控制功能中。我们将使用经过长期自我管理训练的啮齿动物检验这一假设 MDPV十天。拟议的研究旨在解决我们对如何理解的差距 MDPV破坏了认知控制以及哪些大脑区域受到影响最大，并计算连通性 fMRI的大脑变化。在这个项目中，候选人将评估两个认知控制的子过程， 冲动和灵活性。将分析有关该行为有关功能连接性变化的行为 纵向休息状态fMRI（RSFMRI）数据和神经元性能依赖性活性 大鼠调节的细胞骨架相关基因（ARC）mRNA表达。进行拟议的研究将 允许候选人在整合RSFMRI的纵向研究的独立研究职业中招致 连通性，行为和弧细胞分析，分解药物使用障碍的研究。