Lateral septum inputs to nucleus accumbens mediates stress induced suppression of natural reward seeking

Ke Zhang; Yan-Chen Guo; Xiao-Dong Wang; Ying-Jie Zhu; Bing-Xing Pan; Cheng Deng; Ti-Fei Yuan

doi:10.1016/j.phrs.2022.106463

Lateral septum inputs to nucleus accumbens mediates stress induced suppression of natural reward seeking

Pharmacol Res. 2022 Oct:184:106463. doi: 10.1016/j.phrs.2022.106463. Epub 2022 Sep 23.

Authors

Ke Zhang¹, Yan-Chen Guo², Xiao-Dong Wang³, Ying-Jie Zhu⁴, Bing-Xing Pan⁵, Cheng Deng⁶, Ti-Fei Yuan⁷

Affiliations

¹ Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Neurobiology and Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Shenzhen Key Lab of Drug Addiction, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁵ Institute of Life Sciences, Nanchang University, Nanchang, Jiangxi, China.
⁶ Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China; Institutes for Systems Genetics, Frontiers Science Centre for Disease-Related Molecular Network, National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610212, Sichuan, China. Electronic address: dengcheng2014@126.com.
⁷ Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China. Electronic address: ytf0707@126.com.

PMID: 36162602
DOI: 10.1016/j.phrs.2022.106463

Abstract

Stress alters the level of reward evaluation and seeking. However, the neural circuitry mechanisms underlying stress induced effects on natural reward seeking remain unclear. Here we report a septal-accumbens pathway that mediates the effects of acute stress on reward seeking suppression. We first established the sucrose oral self-administration paradigm and measured the effects of acute stress on reward seeking behavior after 21 days of abstinence. Both forced swimming stress and foot shock stress significantly suppressed the natural reward seeking. Among a variety of brain regions, intermediolateral septum (LSi) appear as a strong stress-responsive area containing abundant c-Fos positive cells; chemogenetic inactivation of LSi reinstated the reward seeking behavior. To elucidate the downstream targets receiving LSi projections, we combined pathway-specific retro-labeling and chemogenetic manipulation to confirm the involvement of LSi-nucleus accumbens (NAc) rather than the Ventral tegmental area (VTA) in mediating the observed behavioral responses. In conclusion, the septal-accumbal projection constitute a discrete circuit dictating the stress evoked alterations on reward seeking and may implicate in treatment of stress induced anhedonia.

Keywords: Accumbens; Acute stress; Intermediolateral septum; Self-administration; Septum; Sucrose-seeking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Conditioning, Operant* / physiology
Nucleus Accumbens*
Reward
Sucrose / pharmacology
Ventral Tegmental Area

Substances

Sucrose