Gene Regulation in Memory Circuits as a Consequence of Polysubstance Use

多物质使用导致的记忆电路基因调控

基本信息

批准号：
10739399
负责人：
Karla R. Kaun
金额：
$ 51.29万
依托单位：
BROWN UNIVERSITY
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：
2023-08-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739399
关键词：
Affect Alcohol consumption Alcohols Animals Behavior Behavioral Behavioral Assay Biological Assay Brain CREB1 gene Cells Chromatin Coupled Cues Drosophila genus Drosophila melanogaster Ethanol Functional Imaging Gene Expression Gene Expression Regulation Genes Genetic Transcription Goals Investigation Learning Legal Memory Methamphetamine Molecular Mushroom Bodies Neuronal Plasticity Neurons Nicotine Odors Pathway interactions Pharmaceutical Preparations Process Psychological reinforcement RNA Regulator Genes Role Self Administration Signal Pathway System Testing Transcriptional Regulation Volatilization Work Youth alcohol consequences approach behavior causal variant cocaine use drug of abuse drug seeking behavior experimental study fly gene discovery gene regulatory network individual variation innovation methamphetamine exposure methamphetamine use neural neurogenetics nicotine seeking behavior nicotine self-administration nicotine use opioid use polysubstance use preference psychostimulant response stimulant use synaptic function tool

项目摘要

PROJECT SUMMARY: Methamphetamine is a highly addictive drug that has major effects on the brain’s learning and memory systems. Methamphetamine use is commonly predicted by high use of legal psychostimulants such nicotine or alcohol, but the mechanisms underlying sequential use of alcohol, nicotine and methamphetamine are not well understood. Both nicotine and alcohol alter the function of brain circuits required for adaptive decisions, but the cellular and molecular mechanisms through which this occurs largely remain a mystery. Identifying the gene regulatory networks within select circuits in high alcohol or high nicotine seeking animals and deciphering how methamphetamine alters these networks is necessary to decode the fundamental molecular underpinnings through which methamphetamine influences maladaptive choice. However, the diversity of circuits and cells involved in these responses has confounded our ability to identify key molecular pathways. Our goal is to use a genes-circuits-behavior approach in Drosophila melanogaster to provide an innovative and holistic understanding of the core fundamental principles through which sequential use of psychostimulants alter the molecular landscape and neural dynamics of memory circuits to alter behavioral decisions. Transcriptional regulation within memory circuits is a fundamental process through which psychostimulants drive maladaptive changes in the brain function. This work provides the causal gene regulatory mechanisms through which high preference for alcohol or nicotine affects methamphetamine response in memory circuits. This has major implications for how co-use of psychostimulants alters the molecular landscape that drives drug-seeking behavior.

项目概要：甲基苯丙胺是一种高度成瘾的药物，对大脑的学习和记忆有重大影响甲基苯丙胺的使用通常是通过大量使用合法的精神兴奋剂（例如尼古丁或尼古丁）来预测的。酒精，但连续使用酒精、尼古丁和甲基苯丙胺的机制尚不清楚据了解，尼古丁和酒精都会改变适应性决策所需的大脑回路功能，但这种情况发生的细胞和分子机制在很大程度上仍然是一个谜。寻找高酒精或高尼古丁动物的特定回路内的监管网络并破译如何甲基苯丙胺改变这些网络对于解码基本分子基础是必要的甲基苯丙胺通过其影响适应不良选择然而，电路和细胞的多样性。这些反应的参与混淆了我们识别关键分子途径的能力。果蝇的基因-电路-行为方法提供创新和整体的了解连续使用精神兴奋剂改变精神状态的核心基本原则记忆回路的分子景观和神经动力学改变行为决策。记忆回路内的调节是精神兴奋剂驱动适应不良的基本过程这项工作提供了大脑功能变化的因果基因调节机制。对酒精或尼古丁的偏好会影响记忆回路中的甲基苯丙胺反应。精神兴奋剂的共同使用如何改变驱动药物寻求的分子景观的影响行为。