ArticleProceedings of the National Academy of Sciences of the United States of America2013
Loss of metabotropic glutamate receptor 2 escalates alcohol consumption.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
78 citing papers in PubMed, 118 citations in OpenAlex.
- Article
- Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder.Expert opinion on therapeutic targets · 2026Review
- Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake.Alcohol (Fayetteville, N.Y.) · 2025Review
- mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy.Frontiers in bioscience (Landmark edition) · 2025Review
- Modeling escalation of drug intake to identify molecular targets for treating substance use disorders: A slippery slope upward.Neuroscience and biobehavioral reviews · 2025Review
- Article
- Pleiotropic Effects ofBiomolecules · 2025Review
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Drinking in Male Wistars and P Rats.eNeuro · 2024Article
- Multi-animal-model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking.Alcohol, clinical & experimental research · 2023Article
- Review
- Ketogenic diet: a potential adjunctive treatment for substance use disorders.Frontiers in nutrition · 2023Review
- Genetic and genomic signatures in ethanol withdrawal seizure-prone and seizure-resistant mice implicate genes involved in epilepsy and neuronal excitability.Molecular psychiatry · 2022Article
- Advances in translating mGluPharmacology, biochemistry, and behavior · 2022Review
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- mGlu2 mechanism-based interventions to treat alcohol relapse.Frontiers in pharmacology · 2022Article
- Psilocybin sex-dependently reduces alcohol consumption in C57BL/6J mice.Frontiers in pharmacology · 2022Article
- FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION.Neuroscience and biobehavioral reviews · 2022Review
- Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism.Science advances · 2021Article
- Effects of ceftriaxone on ethanol drinking and GLT-1 expression in ethanol dependence and relapse drinking.Alcohol (Fayetteville, N.Y.) · 2021Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Identification of genes influencing complex traits is hampered by genetic heterogeneity, the modest effect size of many alleles, and the likely involvement of rare and uncommon alleles. Etiologic complexity can be simplified in model organisms. By genomic sequencing, linkage analysis, and functional validation, we identified that genetic variation of Grm2, which encodes metabotropic glutamate receptor 2 (mGluR2), alters alcohol preference in animal models. Selectively bred alcohol-preferring (P) rats are homozygous for a Grm2 stop codon (Grm2 *407) that leads to largely uncompensated loss of mGluR2. mGluR2 receptor expression was absent, synaptic glutamate transmission was impaired, and expression of genes involved in synaptic function was altered. Grm2 *407 was linked to increased alcohol consumption and preference in F2 rats generated by intercrossing inbred P and nonpreferring rats. Pharmacologic blockade of mGluR2 escalated alcohol self-administration in Wistar rats, the parental strain of P and nonpreferring rats. The causal role of mGluR2 in altered alcohol preference was further supported by elevated alcohol consumption in Grm2 (-/-) mice. Together, these data point to mGluR2 as an origin of alcohol preference and a potential therapeutic target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.