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Theranostics 2023; 13(10):3149-3164. doi:10.7150/thno.83079 This issue Cite

Research Paper

Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety-like behaviors and electro-acupuncture therapy

Liying Chen^1,2,*, Zhaoyu Liu^1,*, Ziheng Zhao^1,*, Demin Du¹, Weichao Pan¹, Xiaoyan Wei¹, Jiaxun Nie¹, Feifei Ge¹, Jianhua Ding³, Yu Fan^1,✉, Hee Young Kim^4,✉, Xiaowei Guan^1,✉

1. Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China.
2. Department of Critical Care Medicine, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang, China.
3. Department of Pharmacology, Nanjing Medical University, Nanjing, China.
4. Department of Physiology, Yonsei University College of Medicine, Seoul, South Korea.
*These authors equally contributed to this work

✉ Corresponding authors: guanxw918edu.cn (XG), yfanedu.cn (YF), vet202001ac (HYK). Phone number: +86-25-85811387.

Abstract

Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.

Methods: ACE male mice model were established by exposing to cocaine during adolescent period. Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice. Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1R^CaMKII) in vivo. Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period.

Results: We found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1R^CaMKII levels in claustrum during adulthood. Inhibiting D1R function or knocking-down D1R^CaMKII levels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety-like behaviors in ACE mice during adulthood. EA treatment alleviated ACE-evoked claustrum activation and anxiety-like behaviors by suppressing claustrum D1R^CaMKII.

Conclusion: Our findings identified a novel role of claustrum in ACE-induced anxiety-like behaviors, and put new insight into the D1R^CaMKII in the claustrum. The claustrum D1R^CaMKII might be a promising pharmacological target, such as EA treatment, to treat drug-induced anxiety-like behaviors.

Keywords: Adolescent cocaine exposure, Anxiety, Claustrum, D1R^CaMKII, Electro-acupuncture

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