Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice
Opioid withdrawal generates extremely unpleasant physical symptoms and negative affective states. A rapid relief of opioid withdrawal-induced anxiety has obvious clinical relevance but has been rarely reported. We have shown that injection of ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) lead...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123002942 |
| _version_ | 1797682005209513984 |
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| author | Yuanyuan Chen Peng Yan Shuguang Wei Yongsheng Zhu Jianghua Lai Qiang Zhou |
| author_facet | Yuanyuan Chen Peng Yan Shuguang Wei Yongsheng Zhu Jianghua Lai Qiang Zhou |
| author_sort | Yuanyuan Chen |
| collection | DOAJ |
| description | Opioid withdrawal generates extremely unpleasant physical symptoms and negative affective states. A rapid relief of opioid withdrawal-induced anxiety has obvious clinical relevance but has been rarely reported. We have shown that injection of ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) leads to a rapid alleviation of anxiety-like behaviors in male mice undergoing chronic morphine withdrawal. Here we investigated the contribution of nucleus accumbens shell (sNAc) parvalbumin (PV)-neurons to this process. Chronic morphine withdrawal was associated with higher intrinsic excitability of sNAc PV-neurons via reduced voltage-dependent potassium currents. Chemogenetic inhibition of sNAc PV-neurons reversed the enhanced excitability of PV-neurons and anxiety-like behaviors in these morphine withdrawal male mice, while activation of sNAc PV-neurons induced anxiety-like behaviors in naive male mice. (2R,6R)-HNK reversed the altered potassium currents and intrinsic excitability of sNAc PV-neurons. Our findings demonstrate an important contribution of sNAc PV-neurons to modulating morphine withdrawal-induced anxiety-like behaviors and rapid relief of anxiety-like behaviors by (2R,6R)-HNK, this newly identified target may have therapeutic potentials in treating opioid addiction and anxiety disorders. |
| first_indexed | 2024-03-11T23:53:16Z |
| format | Article |
| id | doaj.art-88c77eb802fe47dc9b06db5479a16781 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-11T23:53:16Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-88c77eb802fe47dc9b06db5479a167812023-09-19T04:09:06ZengElsevierNeurobiology of Disease1095-953X2023-10-01186106279Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male miceYuanyuan Chen0Peng Yan1Shuguang Wei2Yongsheng Zhu3Jianghua Lai4Qiang Zhou5College of Forensic Science, Xi'an Jiaotong University, Xi'an, China; School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, ChinaCollege of Forensic Science, Xi'an Jiaotong University, Xi'an, ChinaCollege of Forensic Science, Xi'an Jiaotong University, Xi'an, ChinaCollege of Forensic Science, Xi'an Jiaotong University, Xi'an, ChinaCollege of Forensic Science, Xi'an Jiaotong University, Xi'an, China; Correspondence to: J Lai, College of Forensic Science, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, China.School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China; Correspondence to: Q Zhou, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, No. 2 Lishui Road, Shenzhen, Guangdong 518055, China.Opioid withdrawal generates extremely unpleasant physical symptoms and negative affective states. A rapid relief of opioid withdrawal-induced anxiety has obvious clinical relevance but has been rarely reported. We have shown that injection of ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) leads to a rapid alleviation of anxiety-like behaviors in male mice undergoing chronic morphine withdrawal. Here we investigated the contribution of nucleus accumbens shell (sNAc) parvalbumin (PV)-neurons to this process. Chronic morphine withdrawal was associated with higher intrinsic excitability of sNAc PV-neurons via reduced voltage-dependent potassium currents. Chemogenetic inhibition of sNAc PV-neurons reversed the enhanced excitability of PV-neurons and anxiety-like behaviors in these morphine withdrawal male mice, while activation of sNAc PV-neurons induced anxiety-like behaviors in naive male mice. (2R,6R)-HNK reversed the altered potassium currents and intrinsic excitability of sNAc PV-neurons. Our findings demonstrate an important contribution of sNAc PV-neurons to modulating morphine withdrawal-induced anxiety-like behaviors and rapid relief of anxiety-like behaviors by (2R,6R)-HNK, this newly identified target may have therapeutic potentials in treating opioid addiction and anxiety disorders.http://www.sciencedirect.com/science/article/pii/S0969996123002942Morphine withdrawalAnxietyNucleus accumbensParvalbumin(2R,6R)-hydroxynorketamine |
| spellingShingle | Yuanyuan Chen Peng Yan Shuguang Wei Yongsheng Zhu Jianghua Lai Qiang Zhou Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice Neurobiology of Disease Morphine withdrawal Anxiety Nucleus accumbens Parvalbumin (2R,6R)-hydroxynorketamine |
| title | Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| title_full | Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| title_fullStr | Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| title_full_unstemmed | Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| title_short | Ketamine metabolite alleviates morphine withdrawal-induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| title_sort | ketamine metabolite alleviates morphine withdrawal induced anxiety via modulating nucleus accumbens parvalbumin neurons in male mice |
| topic | Morphine withdrawal Anxiety Nucleus accumbens Parvalbumin (2R,6R)-hydroxynorketamine |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123002942 |
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