Characterization of Polysubstance Use: Combined Fentanyl and Methamphetamine

多物质使用的特征：芬太尼和甲基苯丙胺的组合

基本信息

批准号：
10607066
负责人：
Monica H Dawes
金额：
$ 4.77万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607066
关键词：
Acute Address Affect Animals Behavior Behavioral Brain Chronic Clinical Complex Cues Data Disease Dopamine Dose Drug Exposure Drug usage Dynorphins Event Exposure to Extinction Feeling Female Fentanyl Fiber Functional disorder Individual Intake Kinetics Laboratories Ligands Measures Methamphetamine Microdialysis Neurobiology Nucleus Accumbens Opioid Opioid Antagonist Periodicity Pharmaceutical Preparations Photometry Population Rattus Reinforcement Schedule Relapse Rewards Rodent Model Role Scanning Schedule Self Administration Sex Differences Signal Transduction Slice Stimulant System Techniques Time United States Withdrawal awake clinically significant dopamine system drug of abuse effective therapy fentanyl self-administration fentanyl use in vivo innovation insight invention kappa opioid receptors male mesolimbic system methamphetamine use mortality norbinaltorphimine novel opioid epidemic opioid overdose opioid use disorder overdose death pharmacologic polysubstance use pre-clinical research receptor function response sensor side effect substance use synthetic opioid transmission process

项目摘要

Project Summary The opioid epidemic currently affecting the United States has entered a new wave of mortality, with combined use of opioid and psychomotor simulants as a major contributing factor to the number of overdose deaths. Combined use of fentanyl and methamphetamine may be due to a number of factors, including greater rewarding effects, decreased negative side effects, and/or feelings that combined use is somehow ‘safer’ than use of fentanyl alone. For those reasons, there is a clear need to examine the differences in the behavioral and neurobiological alterations that occur following chronic use of fentanyl, methamphetamine, and these two substances in combination. My preliminary findings suggest that there is enhanced hypodopaminergia following combined use of fentanyl and methamphetamine (COMBO) when compared to fentanyl use alone. I have determined that 1) in both male and female rats, elicited DA release was decreased in COMBO animals compared to fentanyl alone animals and; (2) male COMBO animals had greater response rates and responded more on a progressive ratio schedule of reinforcement. Therefore, this study aims to investigate the scarcely studied combination of fentanyl and methamphetamine via a three-pronged approach examining behavioral and neurobiological alterations to the DA system through self-administration, microdialysis and fast scan cyclic voltammetry, and the use of the novel photosensor dLight during behavioral responding. Collectively, the proposed aims will provide insight into the neurobiological and behavioral differences elicited by combined use of fentanyl and methamphetamine, an under-studied topic that is highly relevant for the current state of the opioid epidemic in the United States.

项目概要目前影响美国的阿片类药物流行已进入新一波死亡浪潮，加上使用阿片类药物和精神运动模拟剂是导致过量死亡人数的一个主要因素。联合使用芬太尼和甲基苯丙胺可能是由于多种因素造成的，包括更大的奖励效果、负面减少副作用和/或联合使用在某种程度上比“更安全”的感觉由于这些原因，显然需要检查行为和芬太尼的差异。长期使用芬太尼、甲基苯丙胺和这两种药物后发生的神经生物学改变我的初步研究结果表明，多巴胺能减退症会增强。与单独使用芬太尼相比，联合使用芬太尼和甲基苯丙胺 (COMBO) I。已确定 1) 在雄性和雌性大鼠中，COMBO 动物中引发的 DA 释放均减少与单独使用芬太尼的动物相比；(2) 雄性 COMBO 动物有更高的反应率和反应更多关于强化的渐进比例计划因此，本研究旨在调查几乎没有的情况。通过三管齐下的方法研究芬太尼和甲基苯丙胺的组合，检查行为通过自我管理、微透析和快速循环扫描对 DA 系统进行神经生物学改变伏安法，以及在行为响应过程中使用新型光电传感器 dLight。拟议的目标将深入了解联合使用引起的神经生物学和行为差异芬太尼和甲基苯丙胺的问题，这是一个与当前状态高度相关的尚未充分研究的主题美国阿片类药物流行。