IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain
The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to μ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222007351 |
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| author | Shuo Li Xiao-qin Zhang Chuan-chuan Liu Zhi-yuan Wang Guan-yi Lu Hao-wei Shen Ning Wu Jin Li Fei Li |
| author_facet | Shuo Li Xiao-qin Zhang Chuan-chuan Liu Zhi-yuan Wang Guan-yi Lu Hao-wei Shen Ning Wu Jin Li Fei Li |
| author_sort | Shuo Li |
| collection | DOAJ |
| description | The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to μ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo. However, the effects of IRAS on morphine psychological dependence are not fully understood. To extend these studies, we investigated the impact of IRAS on morphine dependence in conditioned place preference (CPP) experiments and explored the underlying mechanisms. Knockout of IRAS enhanced the acquisition and reinstatement of morphine-induced CPP. Conditional-knockout of IRAS in the nucleus accumbens (NAc) reproduced higher CPP, and overexpression of IRAS in the NAc rescued the increased morphine-induced CPP in IRAS-/- mice. IRAS-/- mice showed dramatic cAMP-dependent protein kinase (PKA) activation, upregulation of the phosphorylation of the AMPA receptor GluR1-S845 and NMDA receptor NR1-S897 in the NAc after CPP experiment. Moreover, knockout of IRAS induced an increase in spontaneous excitatory postsynaptic current (sEPSC) frequency and a decrease in the AMPA/NMDA ratio in the NAc after chronic morphine treatment. The selective AMPA receptor antagonist NBQX could inhibit morphine CPP in WT mice, while its effect was significantly reduced in IRAS-/- mice. Together, our results demonstrate that IRAS contributes to the regulation of morphine dependence and that the alteration of glutamatergic transmission in the NAc may participate in the effect of IRAS. |
| first_indexed | 2024-04-13T18:06:17Z |
| format | Article |
| id | doaj.art-3526956b900146658e6bde33eef09a6e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T18:06:17Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-3526956b900146658e6bde33eef09a6e2022-12-22T02:36:03ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113346IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brainShuo Li0Xiao-qin Zhang1Chuan-chuan Liu2Zhi-yuan Wang3Guan-yi Lu4Hao-wei Shen5Ning Wu6Jin Li7Fei Li8State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaDepartment of Pharmacology, School of Medicine, Zhejiang Key Laboratory of Pathophysiology, Ningbo University, 818 Fenghua Rd, Ningbo, Zhejiang 315211, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China; College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaDepartment of Pharmacology, School of Medicine, Zhejiang Key Laboratory of Pathophysiology, Ningbo University, 818 Fenghua Rd, Ningbo, Zhejiang 315211, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, ChinaState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China; Corresponding authors.State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China; Corresponding authors.The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to μ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo. However, the effects of IRAS on morphine psychological dependence are not fully understood. To extend these studies, we investigated the impact of IRAS on morphine dependence in conditioned place preference (CPP) experiments and explored the underlying mechanisms. Knockout of IRAS enhanced the acquisition and reinstatement of morphine-induced CPP. Conditional-knockout of IRAS in the nucleus accumbens (NAc) reproduced higher CPP, and overexpression of IRAS in the NAc rescued the increased morphine-induced CPP in IRAS-/- mice. IRAS-/- mice showed dramatic cAMP-dependent protein kinase (PKA) activation, upregulation of the phosphorylation of the AMPA receptor GluR1-S845 and NMDA receptor NR1-S897 in the NAc after CPP experiment. Moreover, knockout of IRAS induced an increase in spontaneous excitatory postsynaptic current (sEPSC) frequency and a decrease in the AMPA/NMDA ratio in the NAc after chronic morphine treatment. The selective AMPA receptor antagonist NBQX could inhibit morphine CPP in WT mice, while its effect was significantly reduced in IRAS-/- mice. Together, our results demonstrate that IRAS contributes to the regulation of morphine dependence and that the alteration of glutamatergic transmission in the NAc may participate in the effect of IRAS.http://www.sciencedirect.com/science/article/pii/S0753332222007351MorphineIRASNAcCPPAMPARNMDAR |
| spellingShingle | Shuo Li Xiao-qin Zhang Chuan-chuan Liu Zhi-yuan Wang Guan-yi Lu Hao-wei Shen Ning Wu Jin Li Fei Li IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain Biomedicine & Pharmacotherapy Morphine IRAS NAc CPP AMPAR NMDAR |
| title | IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| title_full | IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| title_fullStr | IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| title_full_unstemmed | IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| title_short | IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| title_sort | iras nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain |
| topic | Morphine IRAS NAc CPP AMPAR NMDAR |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222007351 |
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