Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference

Accumulating studies suggest that the glucagon-like peptide-1 receptor agonist exendin-4 (Ex4) and toll-like receptor 4 (TLR4) play a pivotal role in the maladaptive behavior of cocaine. However, few studies have assessed whether Ex4 can facilitate the extinction of drug-associated behavior and atte...

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Autores principales:	Changliang Zhu, Tao Hong, Hailiang Li, Shucai Jiang, Baorui Guo, Lei Wang, Jiangwei Ding, Caibin Gao, Yu Sun, Tao Sun, Feng Wang, Yangyang Wang, Din Wan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cocaine condition place preference extinction reinstatement exendin-4 toll-like receptor 4 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/4e5b145a7fe84190ab49f541401fc428
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spelling	oai:doaj.org-article:4e5b145a7fe84190ab49f541401fc4282021-11-30T19:18:31ZGlucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference1662-513710.3389/fnsys.2021.711750https://doaj.org/article/4e5b145a7fe84190ab49f541401fc4282021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnsys.2021.711750/fullhttps://doaj.org/toc/1662-5137Accumulating studies suggest that the glucagon-like peptide-1 receptor agonist exendin-4 (Ex4) and toll-like receptor 4 (TLR4) play a pivotal role in the maladaptive behavior of cocaine. However, few studies have assessed whether Ex4 can facilitate the extinction of drug-associated behavior and attenuate the reinstatement of cocaine-induced condition place preference (CPP) in mice. The main objective of the present study was to evaluate Ex4’s ability to regulate the extinction and reinstatement of cocaine-induced CPP. C57BL/6 mice were conditioned to either cocaine (20 mg/kg) or an equivalent volume of saline to establish a cocaine-mediated CPP paradigm. To investigate the potential effects of Ex4 on extinction, animals received an intraperitoneal injection of Ex4 either immediately or 6 h after each extinction or only on the test day. The persistence of extinction was measured using the reinstatement paradigm evoked by 10 mg/kg of cocaine. To explore the possible impacts of Ex4 and neuroinflammation on cocaine, the expression levels of TLR4 within the hippocampus was detected using western blotting. As a result, we found that systemic administration of Ex4 immediately after each extinction training, instead of 6 h after each extinction and on the day of extinction test, was capable of facilitating extinction in the confined or non-confined CPP extinction paradigms and blocking the cocaine-primed reinstatement of cocaine-induced CPP. Additionally, we also observed that Ex4 was competent to alleviate TLR4 signaling that has been up-regulated by cocaine. Altogether, our findings indicated that the combination of Ex4 with daily extinction training was sufficient to facilitate extinction of the conditioned behavior, attenuate reinstatement of cocaine-induced CPP and inhibit TLR4 signaling. Thus, Ex4 deserves further investigation as a potential intervention for the treatment of cocaine use disorder.Changliang ZhuChangliang ZhuTao HongHailiang LiShucai JiangShucai JiangBaorui GuoLei WangJiangwei DingCaibin GaoCaibin GaoYu SunTao SunTao SunFeng WangFeng WangYangyang WangDin WanFrontiers Media S.A.articlecocainecondition place preferenceextinctionreinstatementexendin-4toll-like receptor 4Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Systems Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cocaine condition place preference extinction reinstatement exendin-4 toll-like receptor 4 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	cocaine condition place preference extinction reinstatement exendin-4 toll-like receptor 4 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Changliang Zhu Changliang Zhu Tao Hong Hailiang Li Shucai Jiang Shucai Jiang Baorui Guo Lei Wang Jiangwei Ding Caibin Gao Caibin Gao Yu Sun Tao Sun Tao Sun Feng Wang Feng Wang Yangyang Wang Din Wan Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
description	Accumulating studies suggest that the glucagon-like peptide-1 receptor agonist exendin-4 (Ex4) and toll-like receptor 4 (TLR4) play a pivotal role in the maladaptive behavior of cocaine. However, few studies have assessed whether Ex4 can facilitate the extinction of drug-associated behavior and attenuate the reinstatement of cocaine-induced condition place preference (CPP) in mice. The main objective of the present study was to evaluate Ex4’s ability to regulate the extinction and reinstatement of cocaine-induced CPP. C57BL/6 mice were conditioned to either cocaine (20 mg/kg) or an equivalent volume of saline to establish a cocaine-mediated CPP paradigm. To investigate the potential effects of Ex4 on extinction, animals received an intraperitoneal injection of Ex4 either immediately or 6 h after each extinction or only on the test day. The persistence of extinction was measured using the reinstatement paradigm evoked by 10 mg/kg of cocaine. To explore the possible impacts of Ex4 and neuroinflammation on cocaine, the expression levels of TLR4 within the hippocampus was detected using western blotting. As a result, we found that systemic administration of Ex4 immediately after each extinction training, instead of 6 h after each extinction and on the day of extinction test, was capable of facilitating extinction in the confined or non-confined CPP extinction paradigms and blocking the cocaine-primed reinstatement of cocaine-induced CPP. Additionally, we also observed that Ex4 was competent to alleviate TLR4 signaling that has been up-regulated by cocaine. Altogether, our findings indicated that the combination of Ex4 with daily extinction training was sufficient to facilitate extinction of the conditioned behavior, attenuate reinstatement of cocaine-induced CPP and inhibit TLR4 signaling. Thus, Ex4 deserves further investigation as a potential intervention for the treatment of cocaine use disorder.
format	article
author	Changliang Zhu Changliang Zhu Tao Hong Hailiang Li Shucai Jiang Shucai Jiang Baorui Guo Lei Wang Jiangwei Ding Caibin Gao Caibin Gao Yu Sun Tao Sun Tao Sun Feng Wang Feng Wang Yangyang Wang Din Wan
author_facet	Changliang Zhu Changliang Zhu Tao Hong Hailiang Li Shucai Jiang Shucai Jiang Baorui Guo Lei Wang Jiangwei Ding Caibin Gao Caibin Gao Yu Sun Tao Sun Tao Sun Feng Wang Feng Wang Yangyang Wang Din Wan
author_sort	Changliang Zhu
title	Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
title_short	Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
title_full	Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
title_fullStr	Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
title_full_unstemmed	Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
title_sort	glucagon-like peptide-1 agonist exendin-4 facilitates the extinction of cocaine-induced condition place preference
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4e5b145a7fe84190ab49f541401fc428
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Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference

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