Evidence map›Paper›PMID 23995381›Full record

ReviewPsychopharmacology2013

Glutamatergic targets for new alcohol medications.

Andrew Holmes, Rainer Spanagel, John H Krystal

Open access · greenAbstract readReview
In one paragraph

Review in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 4 pooled it
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 4 syntheses or guidelines pooled it, 194 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Trial
  6. Trial
  7. Trial
  8. Trial
  9. Article
  10. Article
  11. Endothelial NMDA Receptor Involvement in Retinal Neurovascular Damage Following Prenatal Alcohol Exposure in a Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  12. Article
  13. An adolescent hangover: astrocyte dysfunction in paraventricular thalamus promotes adult anxiety after alcohol exposure in adolescent mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Serum Metabolite Profile in Progressive Versus Nonprogressive Alcohol-Related Liver Disease: A Cross-Sectional Metabolomics Study.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  19. Article
  20. Pleiotropic Effects ofBiomolecules · 2025
    Review

55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Andrew HolmesLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA, holmesan@mail.nih.gov.
Rainer Spanagel
John H Krystal
National Institute on Alcohol Abuse and Alcoholism · USCentral Institute of Mental Health · DE

Funding

YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAMUL1RR024139 · NCRR · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2006 to 2011
$56.8M
Translational Technologies CoreP50AA012870 · NIAAA · YALE UNIVERSITY · PI Matthew J Girgenti · 2001 to 2026
$43.7M
Mouse models of stress disorders and addictionZIAAA000411 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI HOLMES, ANDREW · 2009 to 2025
$37.7M
Intramural NIH HHS ZIA AA000411NCRR NIH HHS UL1 RR024139NCRR NIH HHS UL1RR024139NIAAA NIH HHS 2P50AA012870NIAAA NIH HHS P50 AA012870
6 · The paper itself

Abstract

rationaleAn increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol's intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism.

objectivesWe discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters.

resultsChronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol.

conclusionsDespite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new treatments for alcoholism.

Indexed as

AlcoholismAnimalsDrug-Seeking BehaviorGlutamic AcidHumansKainic Acid ReceptorsMolecular Targeted TherapyProtein SubunitsReceptors, AMPAReceptors, N-Methyl-D-AspartateSubstance Withdrawal SyndromeGlutamic AcidKainic Acid ReceptorsProtein SubunitsReceptors, AMPAReceptors, N-Methyl-D-Aspartate

Identifiers

PMID23995381
PMCPMC3811052
OpenAlexW2104412023

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.