Metabotropic glutamate receptor 5 (mGluR5) regulation of ethanol sedation, dependence and consumption: Relationship to acamprosate actions
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Recent studies have demonstrated that metabotropic glutamate receptor 5 (mGluR5) antagonists decrease alcohol self-administration and suggest that the anti-craving medication, acamprosate, may also act to decrease mGluR5 function. To address the role of mGluR5 in behavioural actions of ethanol and acamprosate, we compared mutant mice with deletion of the mGluR5 gene and mice treated with a mGluR5 antagonist (MPEP) or acamprosate. Lack of mGluR5 or administration of MPEP reduced the severity of alcohol-induced withdrawal (AW), increased the sedative effect of alcohol (duration of loss of righting reflex; LORR), and increased basal motor activity. The motor stimulation produced by ethanol was blocked by deletion of mGluR5, but not by injection of MPEP. Both acamprosate and MPEP increased ethanol-induced LORR and reduced AW. Importantly, the protective effects of both MPEP and acamprosate on AW were found when the drugs were injected before, but not after, injection of ethanol. This indicates that the drugs prevented development of dependence rather than merely producing an anticonvulsant action. No effects of acamprosate or MPEP on ethanol-induced LORR and AW were found in mGluR5 knockout mice, demonstrating that mGluR5 is required for these actions. mGluR5 null mutant mice showed decreased alcohol consumption in some, but not all, tests. These data show the importance of mGluR5 for several actions of alcohol and support the hypothesis that some effects of acamprosate require mGluR5 signalling.
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Acamprosate acts as an NMDA receptor antagonist and modulates mGluR5 receptors.
“Acamprosate acts as an NMDA receptor antagonist and modulates mGluR5 receptors [54].”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [54]
The Discussion says acamprosate may attenuate NMDA signalling and may inhibit mGluR5 function, supporting a possible role for both pathways. It does not establish that acamprosate acts as an NMDA receptor antagonist or directly modulates mGluR5; it notes that recombinant-receptor studies found no interaction with acamprosate. The discussion of possible direct NMDA blockade concerns MPEP, not acamprosate. (LLM, conf=0.88)
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- Authors
- Blednov, Y. A., & Adron Harris, R.
- Affiliations
- The University of Texas at Austin (US)
- Corresponding author
- Blednov, Yuri A.
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-04-01
- Volume
- 11
- Issue
- 06
- Pages
- 775-93
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC2574715
- OpenAlex
- W2099858791
- Cited by
- 123
- References
- 54
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 15 · 2013: 10 · 2012: 17
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
- National Institutes of Health (5r01aa006399-36)
- U.S. Public Health Service (A06399)
- National Institute on Alcohol Abuse and Alcoholism (R01-AA006399, AA U01 13520, U01AA013520)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- metabotropic glutamate receptor 5, acamprosate, MPEP, ethanol sedation, alcoholism, alcohol self-administration, alcohol consumption, loss of righting reflex, motor stimulation
- MeSH terms
- Acamprosate, Alcohol Deterrents, Alcohol Drinking, Ethanol, Alcoholism, Analysis of Variance, Animals, Behavior, Animal, Central Nervous System Depressants, Choice Behavior, Conditioning, Operant, Dose-Response Relationship, Drug, Drug Interactions, Female, Male, Mice, Inbred C57BL, Motor Activity, Pyridines, Reflex, Self Administration, Sex Factors, Taurine, Receptors, Metabotropic Glutamate, Mice, Knockout, Excitatory Amino Acid Antagonists, Mice, Receptor, Metabotropic Glutamate 5
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