Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol
Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminerg...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.636901/full |
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| author | Hui Chen Dan Xu Yu Zhang Yan Yan JunXiao Liu ChengXi Liu Wei Shen Tian Yu Jin Liu |
| author_facet | Hui Chen Dan Xu Yu Zhang Yan Yan JunXiao Liu ChengXi Liu Wei Shen Tian Yu Jin Liu |
| author_sort | Hui Chen |
| collection | DOAJ |
| description | Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. In vivo GCaMP-based (AVV-hSyn-GCaMP6s) fiber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to confirm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was significantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was significantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP fluorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol. |
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| publishDate | 2021-03-01 |
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| spelling | doaj.art-ec85b1075eff4efbba3349ba62d6d8582022-12-21T22:22:36ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-03-011510.3389/fnins.2021.636901636901Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of PropofolHui Chen0Dan Xu1Yu Zhang2Yan Yan3JunXiao Liu4ChengXi Liu5Wei Shen6Tian Yu7Jin Liu8Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaSchool of Life Sciences and Technology, ShanghaiTech University, Shanghai, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaPropofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. In vivo GCaMP-based (AVV-hSyn-GCaMP6s) fiber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to confirm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was significantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was significantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP fluorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.https://www.frontiersin.org/articles/10.3389/fnins.2021.636901/fullpropofolhedoniclocus ceruleusventral tegmental areachemogeneticfiber photometry |
| spellingShingle | Hui Chen Dan Xu Yu Zhang Yan Yan JunXiao Liu ChengXi Liu Wei Shen Tian Yu Jin Liu Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol Frontiers in Neuroscience propofol hedonic locus ceruleus ventral tegmental area chemogenetic fiber photometry |
| title | Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol |
| title_full | Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol |
| title_fullStr | Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol |
| title_full_unstemmed | Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol |
| title_short | Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol |
| title_sort | neurons in the locus coeruleus modulate the hedonic effects of sub anesthetic dose of propofol |
| topic | propofol hedonic locus ceruleus ventral tegmental area chemogenetic fiber photometry |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.636901/full |
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