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: 10705561
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705561
• 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; Cytoskeleton; Dangerousness; Data; Dopamine; Drug Use Disorder; Exposure to; Functional Magnetic Resonance Imaging; Gene Expression; Genes; Grant; Health Professional; Healthcare; Hour; Impairment; Impulsivity; Information Storage; Intravenous; Knowledge acquisition; 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; Process; Publishing; Rattus; Recreation; Research; Rest; Rewards; Rodent; Self Administration; Social Interaction; Structure; Substance Use Disorder; Task Performances; Techniques; Testing; Thalamic structure; Time; Training; abuse liability; bath salts; behavioral outcome; brain circuitry; career; cognitive change; cognitive control; cognitive function; cognitive process; cognitive testing; cognitive training; design; discounting; drug seeking behavior; environmental change; flexibility; frontal lobe; goal oriented behavior; interest; mRNA Expression; mental set; neural; neuroimaging; neurotransmission; pharmacologic; preference; response; skill acquisition; 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.

摘要