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Study · Animal study (in vivo) · rat · 2020

4 results

Brain Site-Specific Inhibitory Effects of the GLP-1 Analogue Exendin-4 on Alcohol Intake and Operant Responding for Palatable Food.

Colvin KJ, Killen HS, Kanter MJ, Halperin MC, Engel L, Currie PJ

International journal of molecular sciences19 Dec 2020Cited by 52 (Europe PMC)

PMID33352692 (opens in a new tab)PMCIDPMC7766977 (opens in a new tab)DOI10.3390/ijms21249710 (opens in a new tab)PepBankPUB-33352692
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Summary

Approximately 14.4 million Americans are experiencing alcohol use disorder (AUD) and about two-thirds of people who experience drug addiction will relapse, highlighting the need to develop novel and effective treatments. Glucagon-like peptide-1 (GLP-1) is a peptide hormone implicated in the mesocorticolimbic reward system and has become a peptide of interest with respect to its putative inhibitory effects on drug reward. In order to further develop treatments for those diagnosed with AUD, the interplay between GLP-1 receptor signaling and ethanol consumption must be elucidated. In the present study, we investigated the ability of the GLP-1 analogue, exendin-4 (Ex-4), to alter alcohol intake and operant responding for sucrose pellets in order to further understand the role of this compound in mediating reward. We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats. In alcohol investigations, we utilized a two-bottle choice intermittent access protocol. In separate groups of rats, we adopted an operant paradigm in order to examine the effect of Ex-4 on motivated responding for palatable food. Results indicated that GLP-1 receptor signaling effectively suppressed voluntary alcohol intake when injected into the ventral tegmental area (VTA), the accumbens core (NAcC) and shell (NAcS), the dorsomedial hippocampus (DMHipp), and the lateral hypothalamus (LH), which are all structures linked to brain reward mechanisms. The arcuate nucleus (ARcN) and the paraventricular nucleus (PVN) of the hypothalamus were unresponsive, as was the basolateral amygdala (BLA). However, Ex-4 treatment into the ArcN and PVN suppressed operant responding for sucrose pellets. In fact, the VTA, NAcC, NAcS, LH, and the DMHipp all showed comparable suppression of sucrose responding. Overall, our findings suggest that these central structures are implicated in brain reward circuitry, including alcohol and appetitive motivation, which may be mediated by GLP-1 receptor mechanisms. GLP-1, therefore, may play a critical role in modifying addictive behaviors via activation of multiple GLP-1 systems throughout the brain.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In rats, exendin‑4 suppressed voluntary alcohol intake after injection into VTA, NAcC, NAcS, DMHipp and LH.

    In plain wordsIn rats, exendin‑4 suppressed voluntary alcohol intake after injection into VTA, NAcC, NAcS, DMHipp and LH.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAlcohol intake in responsive brain sites
    Study

    ratn: not reported in source

    Male Sprague Dawley rats
    Outcome group
    Addiction, withdrawal and alcohol intake · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Results indicated that GLP-1 receptor signaling effectively suppressed voluntary alcohol intake when injected into the ventral tegmental area (VTA), the accumbens core (NAcC) and shell (NAcS), the dorsomedial hippocampus (DMHipp), and the lateral hypothalamus (LH), which are all structures linked to brain reward mechanisms.
    1 context sentence
    Summary · context
    We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In rats, exendin‑4 did not affect alcohol intake after injection into ARcN, PVN or BLA.

    In plain wordsIn rats, exendin‑4 did not affect alcohol intake after injection into ARcN, PVN or BLA.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeAlcohol intake in unresponsive brain sites
    Study

    ratn: not reported in source

    Male Sprague Dawley rats
    Outcome group
    Addiction, withdrawal and alcohol intake · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The arcuate nucleus (ARcN) and the paraventricular nucleus (PVN) of the hypothalamus were unresponsive, as was the basolateral amygdala (BLA).
    2 context sentences
    Summary · context
    Results indicated that GLP-1 receptor signaling effectively suppressed voluntary alcohol intake when injected into the ventral tegmental area (VTA), the accumbens core (NAcC) and shell (NAcS), the dorsomedial hippocampus (DMHipp), and the lateral hypothalamus (LH), which are all structures linked to brain reward mechanisms.
    Summary · context
    We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In rats, exendin‑4 in ArcN and PVN suppressed operant responding for sucrose pellets.

    In plain wordsIn rats, exendin‑4 in ArcN and PVN suppressed responding for sucrose pellets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseSucrose responding in ArcN and PVN
    Study

    ratn: not reported in source

    Male Sprague Dawley rats
    Outcome group
    Appetite and food intake · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, Ex-4 treatment into the ArcN and PVN suppressed operant responding for sucrose pellets.
    1 context sentence
    Summary · context
    We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In rats, exendin‑4 in VTA, NAcC, NAcS, LH and DMHipp comparably suppressed sucrose responding.

    In plain wordsIn rats, exendin‑4 in VTA, NAcC, NAcS, LH and DMHipp comparably suppressed responding for sucrose.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseSucrose responding in other responsive sites
    Study

    ratn: not reported in source

    Male Sprague Dawley rats
    Outcome group
    Appetite and food intake · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In fact, the VTA, NAcC, NAcS, LH, and the DMHipp all showed comparable suppression of sucrose responding.
    2 context sentences
    Summary · context
    However, Ex-4 treatment into the ArcN and PVN suppressed operant responding for sucrose pellets.
    Summary · context
    We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats.

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

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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