Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin seeking behavior in rats

Douton, Joaquin E.; Augusto, Corinne; Stultzfus, Brooke A; Salli, Nurgul; Vrana, Kent E.; Grigson, Patricia S.

doi:10.1101/730408

Cited by 7 publications

(20 citation statements)

References 81 publications

(106 reference statements)

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“…The discrepant results in the self‐administration paradigm may indicate species differences between rats and mice. Indeed, another rat study reported that exenatide reduced responding for cues previously associated with heroin injections in a reinstatement procedure of operant behaviour (Douton et al, 2021). Treatment with the selective DPP‐4 inhibitor linagliptin was also reported to reduce morphine‐conditioned place preference and facilitate extinction of the morphine preference in rats (Łupina et al, 2020).…”

Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 99%

“…Mechanisms involving some form of satiation would be consistent with the known effects of GLP‐1 system stimulation on the regulation of nutrient intake. However, several studies have reported that GLP‐1 receptor stimulation can suppress drug‐conditioned behaviours, in both classical conditioning (CPP procedures) and operant conditioning (drug seeking using reinstatement procedures), that is, tests during which the drug is unavailable (Douton et al, 2021; Egecioglu, Steensland, et al, 2013; Egecioglu, Engel, & Jerlhag, 2013a, 2013b; Graham et al, 2013; Harasta et al, 2015; Hernandez et al, 2018, 2019, 2020; Shirazi et al, 2013; Sirohi et al, 2016; Vallöf et al, 2016; Vallöf, Kalafateli, et al, 2019; Vallöf, Vestlund, et al, 2019). This would suggest that GLP‐1 receptor stimulation also modulates mechanisms underlying drug and alcohol ‘seeking’ or ‘wanting’, and not only intake and satiation.…”

Section: Possible Mechanisms Of Actionmentioning

confidence: 99%

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The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Klausen

Thomsen

Wörtwein

et al. 2022

British J Pharmacology

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Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon‐like peptide 1 (GLP‐1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP‐1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti‐addiction treatment. Studies in rodents and non‐human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP‐1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered. LINKED ARTICLES This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc

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Section: Role Of Glp‐1 In Substance Use Disordermentioning

confidence: 99%

Section: Possible Mechanisms Of Actionmentioning

confidence: 99%

The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Klausen

Thomsen

Wörtwein

et al. 2022

British J Pharmacology

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“…It is yet unknown that whether this gene delivery platform can reduce reinstatement induced by drug-associated cue or stress. Exendin-4, a GLP1R agonist, can reduce cue-induce heroin-seeking in a self-administration model [ 42 ]. Whether skin-derived GLP1 can reduce cue-elicited drug-seeking needs to be addressed in the future.…”

Section: Discussionmentioning

confidence: 99%

Reducing alcohol and/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform

Kong

Yue

et al. 2021

Mol Psychiatry

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Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.

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“…The impaired ability of post‐escalation AIC‐lesioned rats to reach a stable higher plateau of heroin intake when given extended access may reflect disrupted drug satiety (Steidl, Myal, & Wise, 2015) in an allostatic state in which intake is regulated and maintained around an elevated baseline (Koob & Moal, 1997). The reinforcing and motivational properties of opiates have been shown to depend on systemically released peptides involved in food satiety (Douton et al., 2019) and acute food restriction‐induced heroin seeking depends on leptin and ghrelin (D'Cunha, Chisholm, Hryhorczuk, Fulton, & Shalev, 2020; Shalev, Yap, & Shaham, 2001). Chronic exposure to opiates triggers long‐term adaptations in satiety‐controlling (Duraffourd et al., 2012), enteric neurons (Duraffourd, Kumala, Anselmi, Brecha, & Sternini, 2014) that project via visceral afferent pathways to the insula (Mayer, 2011).…”

Section: Discussionmentioning

confidence: 99%

The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

Joshi

Puaud

Fouyssac

et al. 2020

Eur J of Neuroscience

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The anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug‐related behaviours is complex as in rats exposed to extended access to cocaine self‐administration, the AIC was shown to exert a state‐dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. We investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC induced both prior to or after long‐term exposure to extended access heroin self‐administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham surgeries, pre‐exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.

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Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin seeking behavior in rats

Abstract: Background

Cited by 7 publications

References 81 publications

The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Reducing alcohol and/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform

The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

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