Chloral Hydrate Alters Brain Activation Induced by Methamphetamine-Associated Cue and Prevents Relapse

Chenyu Jiang; Yunlong Xu; Jiafeng Zhong; Junyan Wu; Jian He; Wei Xu; Yingjie Zhu

doi:10.3389/fnmol.2022.934167

Chloral Hydrate Alters Brain Activation Induced by Methamphetamine-Associated Cue and Prevents Relapse

Front Mol Neurosci. 2022 Jul 11:15:934167. doi: 10.3389/fnmol.2022.934167. eCollection 2022.

Authors

Chenyu Jiang^{1

2}, Yunlong Xu^{1

2}, Jiafeng Zhong^{1

2}, Junyan Wu^{1

3

4}, Jian He^{1

5}, Wei Xu^{1

2}, Yingjie Zhu^{1

2

6

7

7}

Affiliations

¹ Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Chinese Academy of Sciences, Shenzhen, China.
² College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
³ The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, China.
⁶ Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁷ CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Abstract

Methamphetamine is a highly addictive drug and its abuse leads to serious health and social problems. Until now, no effective medications are yet available for the treatment of methamphetamine addiction. Our study reveals that chloral hydrate, a clinical sedative drug, suppresses the seeking desire for methamphetamine. After 5 days of continuous administration (subanesthetic dose 50 mg/kg and 100 mg/kg), methamphetamine-seeking behavior of rats was inhibited in the condition place preference and intravenous self-administration tests. Furthermore, chloral hydrate treatment robustly suppressed cue-induced methamphetamine relapse. The whole brain c-fos immunostaining revealed that chloral hydrate treatment suppressed neuronal activity in the rhomboid thalamic nucleus (Rh), dorsal endopiriform nucleus (dEn), and claustrum (Cl) while enhanced zona incerta (ZI) activity during cue-induced methamphetamine relapse. Therefore, chloral hydrate could remodel neural network activity and serve as a potential medicine to treat methamphetamine addiction.

Keywords: addiction; brain activation; chloral hydrate (CH); cue-induced relapse; methamphetamine.