ANKS1B in the Nucleus Accumbens Controls Escalated Cocaine Self‐Administration via Regulating CBP‐FoxO3 Complex
Source abstract
Abstract
ABSTRACT The transition from controlled to escalated drug intake is a core feature of cocaine use disorder (CUD), yet the molecular mechanisms underlying this behavioral escalation remain poorly defined. Our prior genome‐wide association study (GWAS) identified ANKS1B as a significant shared genetic risk factor for heroin, methamphetamine, and alcohol dependence, suggesting a broad role in addiction vulnerability. However, the specific function of ANKS1B in cocaine addiction and its associated neural mechanisms were unknown. Here, we found that ANKS1B expression level in the Nucleus Accumbens (NAc) was downregulated after extended cocaine use, and manipulating ANKS1B could selectively influence the escalation of cocaine intake and the subsequent cocaine‐seeking behavior in the long‐access cocaine self‐administration rat model. Molecular experiments reveal that ANKS1B interacts with the histone acetyltransferase CBP to control H3K27 acetylation and extended cocaine intake, via epigenetically repressing the transcription factor FoxO3. Overall, these findings suggest that ANKS1B is a crucial factor influencing the escalation of cocaine use. The ANKS1B‐CBP‐FoxO3 signaling pathway presents a promising target for potential therapeutic interventions for controlling extended cocaine use.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Neurotransmitter Receptor Influence on Behavior · FOXO transcription factor regulation · Genetic Associations and Epidemiology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Neurobiology School of Basic Medical Sciences National Institute on Drug Dependence Peking University Beijing China
Beijing Key Laboratory of Drug Dependence Research Peking University Beijing China
Peking University Sixth Hospital Peking University Institute of Mental Health Key of Mental Health Ministry of Health (Peking University) National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing China
State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular Pharmacology School of Pharmaceutical Sciences Peking University Beijing China
Shandong Institute of Brain Science and Brain‐inspired Research Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan China
College of Life Sciences and Health Wuhan University of Science and Technology Wuhan Hubei China
School of Basic Medical Sciences Zhengzhou University Zhengzhou China
Hospital of Tsinghua University (Beijing Huaxin Hospital) Beijing China
Peking‐Tsinghua Center for Life Sciences and PKU‐IDG/McGovern Institute for Brain Research Peking University Beijing China
Funding
National Natural Science Foundation of China
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