Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
The histone demethylase KDM6B in the medial prefrontal cortex epigenetically regulates cocaine reward memory
Neuropharmacology, v 141, pp 113-125
01 Oct 2018
PMID: 30165076
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epigenetic remodeling contributes to synaptic plasticity via modification of gene expression, which underlies cocaine-induced long-term memory. A prevailing hypothesis in drug addiction is that drugs of abuse rejuvenate developmental machinery to render reward circuitry highly plastic and thus engender drug memories to be highly stable. Identification and reversal of these pathological pathways are therefore critical for cocaine abuse treatment. Previous studies revealed an interesting finding in which the mRNA of histone lysine demethylase, KDM6B, is upregulated in the medial prefrontal cortex (mPFC) during early cocaine withdrawal. However, whether and how it contributes to drug-seeking behavior remain unknown. Here we used a conditioned place preference paradigm to investigate the potential role of KDM6B in drug-associated memory. We found that KDM6B protein levels selectively increased in the mPFC during cocaine withdrawal. Notably, systemic injection of KDM6B inhibitor, GSK-J4, disrupted both reconsolidation of cocaine-conditioned memory and cocaine-primed reinstatement, suggesting dual effects of KDM6B in cocaine reward memory. In addition, we found that NMDAR expression and function were both enhanced during early cocaine withdrawal in mPFC. Injection of GSK-J4 selectively reversed this cocaine-induced increase of NR2A expression and synaptic function, suggesting that mal-adaptation of cocaine-induced synaptic plasticity in mPFC largely underlies KDM6B-mediated cocaine-associated memory. Altogether, these data suggest that KDM6B plays an essential role in cocaine-associated memory, which mainly acts through enhancing cocaine-induced synaptic plasticity in the mPFC. Our findings revealed a novel role of KDM6B in cocaine-associated memory and inhibition of KDM6B is a potential strategy to alleviate drug-seeking behavior.
Metrics
Details
- Title
- The histone demethylase KDM6B in the medial prefrontal cortex epigenetically regulates cocaine reward memory
- Creators
- Yu-Xiang Zhang - College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA.Rita C. Akumuo - Drexel UniversityRodrigo A. Espana - Drexel UniversityChun-Xia Yan - Xi'an Jiaotong UniversityWen-Jun Gao - Drexel UniversityYan-Chun Li - Drexel University
- Publication Details
- Neuropharmacology, v 141, pp 113-125
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- NSFC 81471820; 81172903 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) R01MH085666 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Commonwealth Universal Research Enhancement (CURE) Program R01D A031900; R01MH085666; R21MH110678 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DA031900 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000447482800011
- Scopus ID
- 2-s2.0-85053072633
- Other Identifier
- 991019167927104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy