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Neural mechanisms regulating cocaine consumption

调节可卡因消耗的神经机制

基本信息

批准号：
10399567
负责人：
Paul E. M. Phillips
金额：
$ 51.97万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10399567
关键词：
Address Animals Attenuated Bilateral Biochemical CREB1 gene CRF receptor type 1 CRISPR/Cas technology Chronic Cocaine Cocaine Abuse Collection Consumption Contralateral Corticotropin-Releasing Hormone Dopamine Drug Regulations Drug usage Dynorphins Female Genes Glean Hour Individual Intake Intravenous Investigation Ipsilateral Modeling Neurons Nucleus Accumbens Opioid Antagonist Pathway interactions Pharmaceutical Preparations Pharmacology Phase Public Health Rattus Receptor Signaling Regulation Research Resolution Side Signal Transduction System Testing Training United States Ventral Tegmental Area Viral Work antagonist base cell type cocaine self-administration cocaine use design dopaminergic neuron experimental study insight kappa opioid receptors knock-down male neural circuit neurochemistry neuromechanism neuroregulation overdose death overdose risk relating to nervous system substance abuser tool transcription factor transmission process

项目摘要

Abstract Cocaine abuse remains a major burden on public health with significant numbers of overdose deaths each year. The proposed work characterizes a neural circuit that underlies the increased drug consumption that takes place by some individuals following chronic drug use. This application leverages previous work demonstrating that corticotropin releasing factor (CRF), dynorphin and dopamine signaling can individually impact drug intake and that each of these systems changes with chronic cocaine use. Specifically, the proposed experiments ask how these three neuromodulatory systems interact with each other in the regulation drug consumption. The working hypothesis is that escalation of drug intake following chronic drug use, comes about through a serial pathway where elevated CRF levels causes an increase in dynorphin which consequently reduces dopamine release, producing escalation. However, the experiments are designed to systematically test the functional connections between each of these nodes in the regulation of cocaine intake and, in doing so, discern between eight competing models of the interactions. Therefore, regardless, of whether the results match the working hypothesis or not, the experiments will yield new insight into the interactions between these systems. This information will inform potential treatment targets for moderating intake in substance abusers and thereby reducing harm.

摘要可卡因滥用仍然是公共卫生的一个主要负担，大量过量死亡每年.这项拟议中的工作描述了一个神经回路，该回路是增加药物的基础。一些人在长期吸毒后发生的消费。此应用程序利用以前的工作表明，促肾上腺皮质激素释放因子（CRF），强啡肽和多巴胺信号可以单独影响药物摄入，这些系统中的每一个都随着慢性可卡因的使用。具体地说，拟议的实验询问这三个神经调节系统如何在调节药物消耗方面相互作用。目前的假设是，长期吸毒后的药物摄入是通过一系列途径发生的，其中CRF升高导致强啡肽增加，从而减少多巴胺的释放，升级然而，实验的目的是系统地测试功能连接在可卡因摄入量的调节中，这些节点中的每一个之间，相互作用的竞争模型。因此，无论结果是否与工作相匹配，无论是否假设，实验都将对这些系统之间的相互作用产生新的见解。这一信息将告知潜在的治疗目标，以减少物质滥用者的摄入量，从而减少危害。