Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

Biological Research

Research Article

Kyle B. Bills¹  Hubert Lee²  Suchan Chang³  Bong Hyo Lee³  Hyung Kyu Kim⁴  Hee Young Kim⁴  Han Byeol Jang⁵  DanBi Ahn⁵  Scott C. Steffensen⁶  Sang Chan Kim⁷ 

[1] Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, 84606, Provo, UT, USA;Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, 77555, Galveston, TX, USA;Department of Physiology, College of Korean Medicine, Daegu Haany University, 42158, Daegu, South Korea;Department of Physiology, Yonsei University College of Medicine, 03722, Seoul, South Korea;Department of Physiology, Yonsei University College of Medicine, 03722, Seoul, South Korea;Department of Physiology, College of Korean Medicine, Daegu Haany University, 42158, Daegu, South Korea;Department of Psychology and Neuroscience, Brigham Young University, 84602, Provo, UT, USA;Medical Research Center, College of Korean Medicine, Daegu Haany University, 38610, Gyeongsan, South Korea;

关键词: Mechanical stimulation (MS);    Cocaine;    Lateral habenula;    Locomotor activity;    Ultrasonic vocalization (USVs);    Optogenetics;   

DOI  :  10.1186/s40659-023-00440-7

 received in 2022-09-27, accepted in 2023-05-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry.ResultsMechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit.ConclusionThese findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

【 授权许可】

CC BY   
© The Author(s) 2023

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