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Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system

View ORCID ProfileSoo Min Lee, Yu Fan, Bonghyo Lee, Sang Chan Kim, Kyle B. Bills, Scott C. Steffensen, Hee Young Kim
doi: https://doi.org/10.1101/2021.11.25.470073
Soo Min Lee
1Emotion, Cognition & Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu 41062, South Korea
3Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea
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  • ORCID record for Soo Min Lee
Yu Fan
2Department of Human Anatomy and Histoembryolgy, Nanjing University of Chinese Medicine, Nanjing 210023, China
3Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea
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Bonghyo Lee
3Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea
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Sang Chan Kim
4Medical Research Center, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea
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Kyle B. Bills
5Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
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Scott C. Steffensen
6Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, USA
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Hee Young Kim
3Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea
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  • For correspondence: hykim@dhu.ac.kr
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Abstract

Nociceptive signals interact with various regions of the brain, including those involved in physical sensation, reward, cognition, and emotion. Emerging evidence points to a role of nociception in the modulation of the mesolimbic reward system. The mechanism by which nociception affects dopamine (DA) signaling and reward is unclear. The lateral hypothalamus (LH) and the lateral habenula (LHb) receive somatosensory inputs and are structurally connected with the mesolimbic DA system. Here we show that the LH-LHb pathway is necessary for nociceptive modulation of this system. Our extracellular single-unit recordings and head-mounted microendoscopic calcium imaging revealed that nociceptive stimulation by tail-pinch excited LHb and LH neurons, which was inhibited by chemical lesion of the LH. Tail-pinch decreased extracellular DA release in the nucleus accumbens ventrolateral shell, which was blocked by disruption of the LH. Furthermore, tail-pinch attenuated cocaine-induced locomotor activity, 50-kHz ultrasonic vocalizations and reinstatement of cocaine-seeking behavior, which was inhibited by chemogenetic silencing of the LH-LHb pathway. Our findings suggest that nociceptive stimulation recruits the LH-LHb pathway to inhibit mesolimbic DA system and drug reinstatement.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 27, 2021.
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Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system
Soo Min Lee, Yu Fan, Bonghyo Lee, Sang Chan Kim, Kyle B. Bills, Scott C. Steffensen, Hee Young Kim
bioRxiv 2021.11.25.470073; doi: https://doi.org/10.1101/2021.11.25.470073
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Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system
Soo Min Lee, Yu Fan, Bonghyo Lee, Sang Chan Kim, Kyle B. Bills, Scott C. Steffensen, Hee Young Kim
bioRxiv 2021.11.25.470073; doi: https://doi.org/10.1101/2021.11.25.470073

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