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Study · Animal study (in vivo) · rat · 2013

2 results

Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward.

Shirazi RH, Dickson SL, Skibicka KP

PloS one16 Apr 2013Cited by 176 (Europe PMC)

PMID23613987 (opens in a new tab)PMCIDPMC3628574 (opens in a new tab)DOI10.1371/journal.pone.0061965 (opens in a new tab)PepBankPUB-23613987
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Summary

Glucagon-like-peptide-1 (GLP-1) is a gut- and neuro-peptide with an important role in the regulation of food intake and glucose metabolism. Interestingly, GLP-1 receptors (GLP-1R) are expressed in key mesolimbic reward areas (including the ventral tegmental area, VTA), innervated by hindbrain GLP-1 neurons. Recently GLP-1 has emerged as a potential regulator of food reward behavior, an effect driven by the mesolimbic GLP-1Rs. Its role in other reward behaviors remains largely unexplored. Since a considerable overlap has been suggested for circuitry controlling reward behavior derived from food and alcohol we hypothesized that GLP-1 and GLP-1Rs could regulate alcohol intake and alcohol reward. We sought to determine whether GLP-1 or its clinically safe stable analogue, Exendin-4, reduce alcohol intake and reward. To determine the potential role of the endogenous GLP-1 in alcohol intake we evaluated whether GLP-1R antagonist, Exendin 9-39, can increase alcohol intake. Furthermore, we set out to evaluate whether VTA GLP-1R activation is sufficient to reduce alcohol intake. Male Wistar rats injected peripherally with GLP-1 or Exendin-4 reduced their alcohol intake in an intermittent access two bottle free choice drinking model. Importantly, a contribution of endogenously released GLP-1 is highlighted by our observation that blockade of GLP-1 receptors alone resulted in an increased alcohol intake. Furthermore, GLP-1 injection reduced alcohol reward in the alcohol conditioned place preference test in mice. To evaluate the neuroanatomical substrate linking GLP-1 with alcohol intake/reward, we selectively microinjected GLP-1 or Exendin 4 into the VTA. This direct stimulation of the VTA GLP-1 receptors potently reduced alcohol intake. Our findings implicate GLP-1R signaling as a novel modulator of alcohol intake and reward. We show for the first time that VTA GLP-1R stimulation leads to reduced alcohol intake. Considering that GLP-1 analogues are already approved for clinical use, this places the GLP system as an exciting new potential therapeutic target for alcohol use disorders.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In male Wistar rats, peripheral exendin‑4 reduced alcohol intake in an intermittent-access drinking model.

    In plain wordsIn rats, peripheral exendin‑4 injections reduced alcohol intake.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAlcohol intake
    Study

    ratn: not reported in source

    Male Wistar rats
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated · Peripheral injectionAs given in this study (rat).

    Source sentences

    Summary
    Male Wistar rats injected peripherally with GLP-1 or Exendin-4 reduced their alcohol intake in an intermittent access two bottle free choice drinking model.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In the alcohol-intake model, exendin‑4 microinjection into the ventral tegmental area reduced alcohol intake.

    In plain wordsIn rats, exendin‑4 injection into the ventral tegmental area reduced alcohol intake.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAlcohol intake
    Study

    ratn: not reported in source

    Male Wistar rats
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated · Ventral tegmental area microinjectionAs given in this study (rat).

    Source sentences

    Summary
    This direct stimulation of the VTA GLP-1 receptors potently reduced alcohol intake.
    1 context sentence
    Summary · context
    To evaluate the neuroanatomical substrate linking GLP-1 with alcohol intake/reward, we selectively microinjected GLP-1 or Exendin 4 into the VTA.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · source ClinicalTrials.gov (opens in a new tab)

Status unknownEarly phase 1NCT02690987

Gut Hormones in Obesity, Nicotine and Alcohol Dependence

Imperial College Londonn = 95Aug 2015 to est. Aug 2020

Obesity · Smoking Cessation · Alcoholism

Trial pageClinicalTrials.govUpdated 13 Feb 2020

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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