Cocaine addiction-like behaviors are associated with long-term changes in gene regulation, energy metabolism, and GABAergic inhibition within the amygdala

Author:

Zhou Jessica L.ORCID,de Guglielmo GiordanoORCID,Ho Aaron J.,Kallupi MarsidaORCID,Li Hai-Ri,Chitre Apurva S.ORCID,Carrette Lieselot LG,George OlivierORCID,Palmer Abraham A.ORCID,McVicker GrahamORCID,Telese FrancescaORCID

Abstract

AbstractThe amygdala contributes to negative emotional states associated with relapse to drug seeking, but the cell type-specific gene regulatory programs that are involved in addiction are unknown. Here we generate an atlas of single nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with low and high cocaine addiction-like behaviors following a prolonged period of abstinence. Between rats with different addiction indexes, there are thousands of cell type-specific differentially expressed genes and these are enriched for molecular pathways including GABAergic synapse in astrocytes, excitatory, and somatostatin neurons. We find that rats with higher addiction severity have excessive GABAergic inhibition in the amygdala, and that hyperpolarizing GABAergic transmission and relapse-like behavior are reversed by pharmacological manipulation of the metabolite methylglyoxal, a GABAA receptor agonist. By analyzing chromatin accessibility, we identify thousands of cell type-specific chromatin sites and transcription factor (TF) motifs where accessibility is associated with addiction-like behaviors, most notably at motifs for pioneer TFs in the FOX, SOX, and helix-loop-helix families.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3