Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction
Abstract Feeding behavior changes induced by opioid addiction significantly contribute to the worsening opioid crisis. Activation of the reward system has shown to provoke binge eating disorder in individuals with opioid use disorder, whereas prolonged opioid exposure leads to weight loss. Understan...
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| Language: | English |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411858 |
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| author | Huiming Li Sa Wang Dan Wang Jiannan Li Ge Song Yongxin Guo Lu Yin Tingting Tong Haopeng Zhang Hailong Dong |
| author_facet | Huiming Li Sa Wang Dan Wang Jiannan Li Ge Song Yongxin Guo Lu Yin Tingting Tong Haopeng Zhang Hailong Dong |
| author_sort | Huiming Li |
| collection | DOAJ |
| description | Abstract Feeding behavior changes induced by opioid addiction significantly contribute to the worsening opioid crisis. Activation of the reward system has shown to provoke binge eating disorder in individuals with opioid use disorder, whereas prolonged opioid exposure leads to weight loss. Understanding the mechanisms underlying these phenomena is essential for addressing this pressing societal issue. This study demonstrates that weight loss resulting from feeding behavior changes during morphine addiction requires the activation of the ventral tegmental area dopamine (DA) system, which suppresses the orexin feeding center. Specifically, DA exerts an inhibitory effect on orexin neurons in the lateral hypothalamus area (LHA) through a feedforward inhibition mediated by GABA neurons in the LHA, involving D1 receptors (D1R) and T‐type Ca2+ channels. Moreover, the morphine addiction‐induced reduction in body weight and food intake can be reversed by the D1R antagonist SCH23390 and chemogenetic silencing of GABA neurons in the LHA. These findings delineate a neuromodulatory mechanism underlying morphine addiction‐associated feeding behavior changes and weight loss. |
| format | Article |
| id | doaj-art-0fb97d8441b64c8ba2bf448dc221677c |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0fb97d8441b64c8ba2bf448dc221677c2025-08-20T03:10:53ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202411858Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine AddictionHuiming Li0Sa Wang1Dan Wang2Jiannan Li3Ge Song4Yongxin Guo5Lu Yin6Tingting Tong7Haopeng Zhang8Hailong Dong9Department of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaKey Laboratory of Anesthesiology (The Fourth Military Medical University) Ministry of Education of China Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaDepartment of Anesthesiology and Perioperative Medicine Xijing Hospital The Fourth Military Medical University Xi'an 710032 ChinaAbstract Feeding behavior changes induced by opioid addiction significantly contribute to the worsening opioid crisis. Activation of the reward system has shown to provoke binge eating disorder in individuals with opioid use disorder, whereas prolonged opioid exposure leads to weight loss. Understanding the mechanisms underlying these phenomena is essential for addressing this pressing societal issue. This study demonstrates that weight loss resulting from feeding behavior changes during morphine addiction requires the activation of the ventral tegmental area dopamine (DA) system, which suppresses the orexin feeding center. Specifically, DA exerts an inhibitory effect on orexin neurons in the lateral hypothalamus area (LHA) through a feedforward inhibition mediated by GABA neurons in the LHA, involving D1 receptors (D1R) and T‐type Ca2+ channels. Moreover, the morphine addiction‐induced reduction in body weight and food intake can be reversed by the D1R antagonist SCH23390 and chemogenetic silencing of GABA neurons in the LHA. These findings delineate a neuromodulatory mechanism underlying morphine addiction‐associated feeding behavior changes and weight loss.https://doi.org/10.1002/advs.202411858body weightdopaminefeedforward inhibitionfeeding behaviorsmorphine addictionneural circuits |
| spellingShingle | Huiming Li Sa Wang Dan Wang Jiannan Li Ge Song Yongxin Guo Lu Yin Tingting Tong Haopeng Zhang Hailong Dong Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction Advanced Science body weight dopamine feedforward inhibition feeding behaviors morphine addiction neural circuits |
| title | Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction |
| title_full | Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction |
| title_fullStr | Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction |
| title_full_unstemmed | Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction |
| title_short | Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction |
| title_sort | dopamine drives feedforward inhibition to orexin feeding system mediating weight loss induced by morphine addiction |
| topic | body weight dopamine feedforward inhibition feeding behaviors morphine addiction neural circuits |
| url | https://doi.org/10.1002/advs.202411858 |
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