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Nociceptive Stimuli Activate the Hypothalamus–Habenula Circuit to Inhibit the Mesolimbic Reward System and Cocaine-Seeking Behaviors.

Authors :
Soo Min Lee
Han Byeol Jang
Yu Fan
Bong Hyo Lee
Sang Chan Kim
Bills, Kyle B.
Steffensen, Scott C.
Hee Young Kim
Source :
Journal of Neuroscience; 12/7/2022, Vol. 42 Issue 49, p9180-9192, 13p
Publication Year :
2022

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 using male Sprague Dawley rats. 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 increased activity of GABA neurons in ventral tegmental area, decreased the extracellular DA level in the nucleus accumbens ventrolateral shell in intact rats, and reduced cocaine-increased DA concentration, which was blocked by disruption of the LH. Furthermore, tail pinch attenuated cocaine-induced locomotor activity, 22 and 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02706474
Volume :
42
Issue :
49
Database :
Complementary Index
Journal :
Journal of Neuroscience
Publication Type :
Academic Journal
Accession number :
160720184
Full Text :
https://doi.org/10.1523/JNEUROSCI.0577-22.2022