Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice
A high percentage of relapse to compulsive cocaine-taking and cocaine-seeking behaviors following abstinence constitutes a major obstacle to the clinical treatment of cocaine addiction. Thus, there is a substantial need to develop effective pharmacotherapies for the prevention of cocaine relapse. Th...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.769664/full |
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| author | Changliang Zhu Changliang Zhu Lei Wang Jiangwei Ding Hailiang Li Hailiang Li Din Wan Yangyang Sun Baorui Guo Zhenquan He Xiaofan Ren Shucai Jiang Shucai Jiang Caibing Gao Caibing Gao Hua Guo Tao Sun Tao Sun Feng Wang Feng Wang |
| author_facet | Changliang Zhu Changliang Zhu Lei Wang Jiangwei Ding Hailiang Li Hailiang Li Din Wan Yangyang Sun Baorui Guo Zhenquan He Xiaofan Ren Shucai Jiang Shucai Jiang Caibing Gao Caibing Gao Hua Guo Tao Sun Tao Sun Feng Wang Feng Wang |
| author_sort | Changliang Zhu |
| collection | DOAJ |
| description | A high percentage of relapse to compulsive cocaine-taking and cocaine-seeking behaviors following abstinence constitutes a major obstacle to the clinical treatment of cocaine addiction. Thus, there is a substantial need to develop effective pharmacotherapies for the prevention of cocaine relapse. The reinstatement paradigm is known as the most commonly used animal model to study relapse in abstinent human addicts. The primary aim of this study is to investigate the potential effects of systemic administration of glucagon-like peptide-1 receptor agonist (GLP-1RA) exendin-4 (Ex4) on the cocaine- and stress-triggered reinstatement of cocaine-induced conditioned place preference (CPP) in male C57BL/6J mice. The biased CPP paradigm was induced by alternating administration of saline and cocaine (20 mg/kg), followed by extinction training and then reinstatement by either a cocaine prime (10 mg/kg) or exposure to swimming on the reinstatement test day. To examine the effects of Ex4 on the reinstatement, Ex4 was systemically administered 1 h after the daily extinction session. Additionally, we also explored the associated molecular basis of the behavioral effects of Ex4. The expression of nuclear factor κβ (NF-κβ) in the nucleus accumbens (NAc) was detected using Western blotting. As a result, all animals that were treated with cocaine during the conditioning period successfully acquired CPP, and their CPP response was extinguished after 8 extinction sessions. Furthermore, the animals that were exposed to cocaine or swimming on the reinstatement day showed a significant reinstatement of CPP. Interestingly, systemic pretreatment with Ex4 was sufficient to attenuate cocaine- and stress-primed reinstatement of cocaine-induced CPP. Additionally, the expression of NF-κβ, which was upregulated by cocaine, was normalized by Ex4 in the cocaine-experienced mice. Altogether, our study reveals the novel effect of Ex4 on the reinstatement of cocaine-induced CPP and suggests that GLP-1R agonists appear to be highly promising drugs in the treatment of cocaine use disorder. |
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| last_indexed | 2024-04-11T20:40:57Z |
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| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-b83e9a3a3e4a4934ba6f1a3873ada75d2022-12-22T04:04:13ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-01-011510.3389/fnbeh.2021.769664769664Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in MiceChangliang Zhu0Changliang Zhu1Lei Wang2Jiangwei Ding3Hailiang Li4Hailiang Li5Din Wan6Yangyang Sun7Baorui Guo8Zhenquan He9Xiaofan Ren10Shucai Jiang11Shucai Jiang12Caibing Gao13Caibing Gao14Hua Guo15Tao Sun16Tao Sun17Feng Wang18Feng Wang19Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaA high percentage of relapse to compulsive cocaine-taking and cocaine-seeking behaviors following abstinence constitutes a major obstacle to the clinical treatment of cocaine addiction. Thus, there is a substantial need to develop effective pharmacotherapies for the prevention of cocaine relapse. The reinstatement paradigm is known as the most commonly used animal model to study relapse in abstinent human addicts. The primary aim of this study is to investigate the potential effects of systemic administration of glucagon-like peptide-1 receptor agonist (GLP-1RA) exendin-4 (Ex4) on the cocaine- and stress-triggered reinstatement of cocaine-induced conditioned place preference (CPP) in male C57BL/6J mice. The biased CPP paradigm was induced by alternating administration of saline and cocaine (20 mg/kg), followed by extinction training and then reinstatement by either a cocaine prime (10 mg/kg) or exposure to swimming on the reinstatement test day. To examine the effects of Ex4 on the reinstatement, Ex4 was systemically administered 1 h after the daily extinction session. Additionally, we also explored the associated molecular basis of the behavioral effects of Ex4. The expression of nuclear factor κβ (NF-κβ) in the nucleus accumbens (NAc) was detected using Western blotting. As a result, all animals that were treated with cocaine during the conditioning period successfully acquired CPP, and their CPP response was extinguished after 8 extinction sessions. Furthermore, the animals that were exposed to cocaine or swimming on the reinstatement day showed a significant reinstatement of CPP. Interestingly, systemic pretreatment with Ex4 was sufficient to attenuate cocaine- and stress-primed reinstatement of cocaine-induced CPP. Additionally, the expression of NF-κβ, which was upregulated by cocaine, was normalized by Ex4 in the cocaine-experienced mice. Altogether, our study reveals the novel effect of Ex4 on the reinstatement of cocaine-induced CPP and suggests that GLP-1R agonists appear to be highly promising drugs in the treatment of cocaine use disorder.https://www.frontiersin.org/articles/10.3389/fnbeh.2021.769664/fullcocainereinstatementexendin-4pretreatmentnuclear factor κβconditioned place preference |
| spellingShingle | Changliang Zhu Changliang Zhu Lei Wang Jiangwei Ding Hailiang Li Hailiang Li Din Wan Yangyang Sun Baorui Guo Zhenquan He Xiaofan Ren Shucai Jiang Shucai Jiang Caibing Gao Caibing Gao Hua Guo Tao Sun Tao Sun Feng Wang Feng Wang Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice Frontiers in Behavioral Neuroscience cocaine reinstatement exendin-4 pretreatment nuclear factor κβ conditioned place preference |
| title | Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice |
| title_full | Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice |
| title_fullStr | Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice |
| title_full_unstemmed | Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice |
| title_short | Effects of Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 on the Reinstatement of Cocaine-Mediated Conditioned Place Preference in Mice |
| title_sort | effects of glucagon like peptide 1 receptor agonist exendin 4 on the reinstatement of cocaine mediated conditioned place preference in mice |
| topic | cocaine reinstatement exendin-4 pretreatment nuclear factor κβ conditioned place preference |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.769664/full |
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