Cited by 197Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and Outcomes

The DOI matches its Crossref record; 223 of the 223 references it cites were found in a registry or an index.

Glutamatergic targets for new alcohol medications

Open access

Holmes, Andrew, Spanagel, Rainer, Krystal, John H.·2013·Psychopharmacology

DOI 10.1007/s00213-013-3226-2PMC PMC3811052

Open this paper in CoChat — free account

Abstract

Rationale An 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.Objectives We 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.Results Chronic 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.Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new treatments for alcoholism.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s00213-013-3226-2

Cites

223 of 223 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Lim, S. S., Vos, T., Flaxman, A. D., Danaei, G., Shibuya, K., Adair-Rohani, H., AlMazroa, M. A., Amann, M., Anderson, H. R., Andrews, K. G., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61766-8 · Cited by 11,805
Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders
Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon, Y., & Patra, J. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60746-7 · Cited by 3,870
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence: The COMBINE Study: A Randomized Controlled Trial
Anton, R. F., O’Malley, S. S., Ciraulo, D. A., Cisler, R. A., Couper, D., Donovan, D. M., Gastfriend, D. R., Hosking, J. D., Johnson, B. A., LoCastro, J. S., et al. (2006) · JAMA · doi:10.1001/jama.295.17.2003 · Cited by 1,930
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
Moghaddam, B., Adams, B., Verma, A., & Daly, D. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02921.1997 · Cited by 1,793
Ethanol Inhibits NMDA-Activated Ion Current in Hippocampal Neurons
Lovinger, D. M., White, G., & Weight, F. F. (1989) · Science · doi:10.1126/science.2467382 · Cited by 1,448
Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
Patil, S. T., Zhang, L., Martenyi, F., Lowe, S. L., Jackson, K. A., Andreev, B. V., Avedisova, A. S., Bardenstein, L. M., Gurovich, I. Y., Morozova, M. A., et al. (2007) · Nature Medicine · doi:10.1038/nm1632 · Cited by 1,040
Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis
Coyle, J. T. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9062-8 · Cited by 917
Drug Addiction as a Pathology of Staged Neuroplasticity
Kalivas, P. W., & O’Brien, C. P. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301564 · Cited by 761
Oral topiramate for treatment of alcohol dependence: A randomised controlled trial
Johnson, B. A., Ait-Daoud, N., Bowden, C. L., DiClemente, C. C., Roache, J. D., Lawson, K., Javors, M. A., & Ma, J. Z. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13370-3 · Cited by 743
Unveiling the Functions of Presynaptic Metabotropic Glutamate Receptors in the Central Nervous System
Schoepp, D. D. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29296-x · Cited by 693

Show all 221 references

Sorted by citations

Hazardous drinking and alcohol use disorders
MacKillop, J. M., Agabio, R., Ewing, S. W. F., Heilig, M. A., Kelly, J. F., Leggio, L., Lingford-Hughes, A. R., Palmer, A. A., Parry, C. D. H., Ray, L. A., et al. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00406-1 · Cited by 251
Potential Role of N-Acetylcysteine in the Management of Substance Use Disorders
McClure, E. A., Gipson, C. D., Malcolm, R. J., Kalivas, P. W., & Gray, K. M. (2014) · CNS Drugs · doi:10.1007/s40263-014-0142-x · Cited by 200
Structural and functional plasticity of dendritic spines – root or result of behavior?
Gipson, C. D., & Olive, M. F. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12324 · Cited by 214
Molecular mechanisms underlying alcohol-drinking behaviours
Ron, D., & Barak, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.85 · Cited by 165
The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy
Bukke, V. N., Archana, M., Villani, R., Romano, A. D., Wawrzyniak, A., Balawender, K., Orkisz, S., Beggiato, S., Serviddio, G., & Cassano, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207452 · Cited by 161
Targeting glutamate uptake to treat alcohol use disorders
Rao, P. S. S., Bell, R. L., Engleman, E. A., & Sari, Y. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00144 · Cited by 136
Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption
Cheng, Y., Huang, C. C., Ma, T., Wei, X., Wang, X., Lu, J., & Wang, J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.016 · Cited by 135
Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes
Mann, K. F., Roos, C. R., Hoffmann, S., Nakovics, H., Leménager, T., Heinz, A., & Witkiewitz, K. A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.282 · Cited by 131
Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis
Choi, W., Kim, H., Kim, M., Çınar, R., Yi, H., Eun, H. S., Kim, S., Choi, Y. J., Lee, Y., Kim, S. Y., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.001 · Cited by 98
Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism
Meinhardt, M. W., Pfarr, S., Fouquet, G., Rohleder, C., Meinhardt, M. L., Barroso-Flores, J., Hoffmann, R., Jeanblanc, J., Paul, E., Wagner, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abh2399 · Cited by 89
Self-citation
Postdependent state in rats as a model for medication development in alcoholism
Meinhardt, M. W., & Sommer, W. H. (2014) · Addiction Biology · doi:10.1111/adb.12187 · Cited by 87
Cluster and meta‐analyses on factors influencing stress‐induced alcohol drinking and relapse in rodents
Noori, H. R., Helinski, S., & Spanagel, R. (2014) · Addiction Biology · doi:10.1111/adb.12125 · Cited by 79
Self-citation
Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders
Hammond, C. J., Niciu, M. J., Drew, S., & Arias, A. J. (2015) · CNS Drugs · doi:10.1007/s40263-015-0240-4 · Cited by 77
Repeated Binge Drinking Increases Perineuronal Nets in the Insular Cortex
Chen, H., He, D., & Lasek, A. W. (2015) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.12847 · Cited by 77
Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior
Stefaniuk, M., Beroun, A., Lebitko, T., Markina, O. A., Łęski, S., Meyza, K. Z., Grzywacz, A., Samochowiec, J., Samochowiec, A., Radwańska, K., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.026 · Cited by 70
Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine
Enoch, M., Rosser, A. A., Zhou, Z., Mash, D. C., Yuan, Q., & Goldman, D. A. (2014) · Genes Brain & Behavior · doi:10.1111/gbb.12179 · Cited by 70
Do specific NMDA receptor subunits act as gateways for addictive behaviors?
Hopf, F. W. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12348 · Cited by 66
Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition
Burnett, E. J., Chandler, L. J., & Trantham‐Davidson, H. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.08.012 · Cited by 66
Treatment of Comorbid Alcohol Dependence and Anxiety Disorder: Review of the Scientific Evidence and Recommendations for Treatment
Gimeno, C. P., Dorado, M. L., Roncero, C., Szerman, N., Vega, P., Balanzá‐Martínez, V., & Alvarez, E. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00173 · Cited by 63
From Pleasure to Pain, and Back Again: The Intricate Relationship Between Alcohol and Nociception
Robins, M. T., Heinricher, M. M., & Ryabinin, A. E. (2019) · Alcohol and Alcoholism · doi:10.1093/alcalc/agz067 · Cited by 63
Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window
Mihov, Y., & Hasler, G. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw002 · Cited by 56
Metabotropic glutamate receptor 5 binding in male patients with alcohol use disorder
Akkus, F., Mihov, Y., Treyer, V., Ametamey, S. M., Johayem, A., Senn, S., Rösner, S., Buck, A., & Hasler, G. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0066-6 · Cited by 56
GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1
Šerý, O., Sultana, N., Kashem, M. A., Pow, D. V., & Balcar, V. J. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1605-2 · Cited by 52
Reprogramming of mPFC transcriptome and function in alcohol dependence
Heilig, M. A., Barbier, E., Johnstone, A. L., Tapocik, J. D., Meinhardt, M. W., Pfarr, S., Wahlestedt, C., & Sommer, W. H. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12344 · Cited by 54
On the Neurobiological Role of Oxidative Stress in Alcohol-Induced Impulsive, Aggressive and Suicidal Behavior
Tobore, T. O. (2019) · Substance Use & Misuse · doi:10.1080/10826084.2019.1645179 · Cited by 50
Glutamate Receptors within the Mesolimbic Dopamine System Mediate Alcohol Relapse Behavior
Eisenhardt, M., Leixner, S., Luján, R., Spanagel, R., & Bilbao, A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2970-15.2015 · Cited by 49
Self-citation
Interactions Between Alcohol and the Endocannabinoid System
Kunos, G. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14306 · Cited by 50
Reward, Relief and Habit Drinking: Initial Validation of a Brief Assessment Tool
Grodin, E. N., Bujarski, S., Venegas, A., Baskerville, W., Nieto, S. J., Jentsch, D., & Ray, L. A. (2019) · Alcohol and Alcoholism · doi:10.1093/alcalc/agz075 · Cited by 48
Too Difficult to Stop: Mechanisms Facilitating Relapse in Alcohol Dependence
Garbusow, M., Sebold, M., Beck, A., & Heinz, A. (2014) · Neuropsychobiology · doi:10.1159/000362838 · Cited by 47
Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways
Meyers, J. L., Salling, M. C., Almli, L. M., Ratanatharathorn, A. D., Uddin, M., Galea, S., Wildman, D. E., Aiello, A. E., Bradley, B., Ressler, K. J., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.70 · Cited by 42
The Need for Treatment Responsive Translational Biomarkers in Alcoholism Research
Heilig, M. A., Sommer, W. H., & Spanagel, R. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_5006 · Cited by 45
Self-citation
Synaptic plasticity mechanisms common to learning and alcohol use disorderPreprint
Lovinger, D. M., & Abrahao, K. P. (2018) · Learning & Memory · doi:10.1101/lm.046722.117 · Cited by 47
Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective
Hwa, L., Besheer, J., & Kash, T. (2017) · F1000Research · doi:10.12688/f1000research.9609.1 · Cited by 39
GRIK1 Genotype moderates topiramate's effects on daily drinking level, expectations of alcohol's positive effects and desire to drink
Kranzler, H. R., Armeli, S., Feinn, R., Tennen, H. A., Gelernter, J. E., & Covault, J. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000510 · Cited by 40
Chronic alcohol alters rewarded behaviors and striatal plasticity
DePoy, L. M., Daut, R. A., Wright, T., Camp, M., Crowley, N. A., Noronha, B., Lovinger, D. M., & Holmes, A. (2014) · Addiction Biology · doi:10.1111/adb.12131 · Cited by 39
Self-citation
Withdrawal effects following repeated ethanol exposure are prevented by N-acetylcysteine in zebrafish
Mocelin, R., Marcon, M., Araújo, A. S. D. R., Herrmann, A. P., & Piato, Â. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.03.014 · Cited by 39
Neuronal extracellular signal-regulated kinase (ERK) activity as marker and mediator of alcohol and opioid dependence
Zamora-Martinez, E. R., & Edwards, S. (2014) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2014.00024 · Cited by 37
N‐Methyl‐ d ‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers
Krishnan‐Sarin, S., O’Malley, S. S., Franco, N., Cavallo, D. A., Morean, M. E., Shi, J. M., Pittman, B. P., & Krystal, J. H. (2015) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12619 · Cited by 37
Self-citation
Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse
Vengeliene, V., Cannella, N., Takahashi, T. T., & Spanagel, R. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4384-9 · Cited by 37
Self-citation
Evaluation of Guanfacine as a Potential Medication for Alcohol Use Disorder in Long-Term Drinking Rats: Behavioral and Electrophysiological Findings
Fredriksson, I., Jayaram-Lindström, N., Wirf, M., Nylander, E., Nyström, E., Jardemark, K., & Steensland, P. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.294 · Cited by 35
Heavy alcohol use in adolescence is associated with altered cortical activity: a combined TMS–EEG study
Kaarre, O., Kallioniemi, E., Könönen, M., Tolmunen, T., Kekkonen, V., Kivimäki, P., Heikkinen, N., Ferreri, F., Laukkanen, E., & Määttä, S. (2016) · Addiction Biology · doi:10.1111/adb.12486 · Cited by 33
Homer2 regulates alcohol and stress cross-sensitization
Quadir, S. G., dos Santos, J. R. B., Campbell, R. R., Wroten, M. G., Singh, N., Holloway, J. J., Bal, S. K., Camarini, R., & Szumlinski, K. K. (2015) · Addiction Biology · doi:10.1111/adb.12252 · Cited by 37
mGlu5-dependent modulation of anxiety during early withdrawal from binge-drinking in adult and adolescent male mice
Lee, K. M., Coelho, M. A., Class, M. A., & Szumlinski, K. K. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.10.031 · Cited by 32
FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties
Wolfe, S. A., Workman, E. R., Heaney, C. F., Niere, F., Namjoshi, S. V., Cacheaux, L. P., Farris, S. P., Drew, M. R., Zemelman, B. V., Harris, R. A., et al. (2016) · Nature Communications · doi:10.1038/ncomms12867 · Cited by 31
Long‐lasting effect of NMDA receptor antagonist memantine on ethanol‐cue association and relapse
Vengeliene, V., Olevska, A., & Spanagel, R. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13350 · Cited by 31
Self-citation
Decreased anxiety, voluntary ethanol intake and ethanol-induced CPP acquisition following activation of the metabotropic glutamate receptor 8 “mGluR8”
Bahí, A. (2017) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2017.03.004 · Cited by 31
Recovery of Decreased Metabotropic Glutamate Receptor 5 Availability in Abstinent Alcohol-Dependent Patients
Ceccarini, J., Leurquin‐Sterk, G., Crunelle, C. L., de Laat, B., Bormans, G. M., Peuskens, H., & Laere, K. V. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.228825 · Cited by 32
Both ketamine and NBQX attenuate alcohol drinking in male Wistar rats
Kučerová, J., Babinská, Z., Ľupták, M., Getachew, B., & Tizabi, Y. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.12.055 · Cited by 30
How Imaging Glutamate, γ‐Aminobutyric Acid, and Dopamine Can Inform the Clinical Treatment of Alcohol Dependence and Withdrawal
Hillmer, A. T., Mason, G. F., Fucito, L. M., O’Malley, S. S., & Cosgrove, K. (2015) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12893 · Cited by 32
Different sites of alcohol action in the NMDA receptor GluN2A and GluN2B subunits
Zhao, Y., Ren, H., Dwyer, D. S., & Peoples, R. W. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.05.018 · Cited by 29
Memantine reduces alcohol drinking but not relapse in alcohol‐dependent rats
Alaux‐Cantin, S., Buttolo, R., Houchi, H., Jeanblanc, J., & Naassïla, M. (2014) · Addiction Biology · doi:10.1111/adb.12177 · Cited by 32
Problem Drinking, Alcohol Expectancy, and Thalamic Resting-State Functional Connectivity in Nondependent Adult Drinkers
Zhornitsky, S., Ide, J. S., Wang, W., Chao, H. H., Zhang, S., Hu, S., Krystal, J. H., & Li, C. R. (2018) · Brain Connectivity · doi:10.1089/brain.2018.0633 · Cited by 30
Self-citation
Cortical GluN2B deletion attenuates punished suppression of food reward-seeking
Radke, A. K., Nakazawa, K., & Holmes, A. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4033-8 · Cited by 29
Self-citation
Ketamine Differentially Attenuates Alcohol Intake in Male Versus Female Alcohol Preferring (P) Rats
Rezvani, A. H., Levin, E. D., Cauley, M. C., Getachew, B., & Tizabi, Y. (2017) · Journal of Drug and Alcohol Research · doi:10.4303/jdar/236030 · Cited by 28
Novel medications for problematic alcohol use
Heilig, M. A., Witkiewitz, K. A., Ray, L. A., & Leggio, L. (2024) · Journal of Clinical Investigation · doi:10.1172/jci172889 · Cited by 28
Alcohol-Induced Oxidative Stress and Gut–Liver–Brain Crosstalk: Expanding the Paradigm from ALD to MetALD
Lee, J., Jee, Y.-M., Yang, K., & Ryu, T. (2025) · Antioxidants · doi:10.3390/antiox14101196 · Cited by 31
What the alcohol doctor ordered from the neuroscientist
Heilig, M., & Leggio, L. (2016) · Progress in Brain Research · doi:10.1016/bs.pbr.2015.07.023 · Cited by 25
Altered NMDA receptor subunit gene expression in brains of mice showing high vs. low sensitization to ethanol
Nona, C. N., Li, R., & Nóbrega, J. N. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.11.037 · Cited by 25
NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION
Matošić, A. (2016) · Acta Clinica Croatica · doi:10.20471/acc.2016.55.01.19 · Cited by 25
Autophosphorylation of alpha isoform of calcium/calmodulin‐dependent kinase II regulates alcohol addiction‐related behaviors
Harda, Z., Łukasiewicz, K., Ziółkowska, M., Lipiński, M., Cały, A., Matuszek, Ż., Łęski, S., & Radwańska, K. (2015) · Addiction Biology · doi:10.1111/adb.12327 · Cited by 25
Effect of Intravenous Ethanol on Capsaicin-Induced Hyperalgesia in Human Subjects
Arout, C. A., Perrino, A. C., Ralevski, E., Acampora, G. A., Koretski, J. A., Limoncelli, D., Newcomb, J., & Petrakis, I. L. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13095 · Cited by 23
GluN2B Subunit of the NMDA Receptor: The Keystone of the Effects of Alcohol During Neurodevelopment
Naassïla, M., & Pierrefiche, O. (2018) · Neurochemical Research · doi:10.1007/s11064-017-2462-y · Cited by 23
Do Alcohol-Related AMPA-Type Glutamate Receptor Adaptations Promote Intake?
Hopf, F. W., & Mangieri, R. A. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_105 · Cited by 20
Ginsenoside Rg1 alleviates repeated alcohol exposure-induced psychomotor and cognitive deficits
Huang, L., Zhuang, P., Lü, C., Chen, Y., Lv, J., Qin, M., Liao, D., Liu, X., & Shi, Z. (2020) · Chinese Medicine · doi:10.1186/s13020-020-00325-x · Cited by 23
Pharmacotherapeutic options for co-morbid depression and alcohol dependence
Hillemacher, T., & Frieling, H. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1561870 · Cited by 24
Psychedelic Targeting of Metabotropic Glutamate Receptor 2 and Its Implications for the Treatment of Alcoholism
Domanegg, K., Sommer, W. H., & Meinhardt, M. W. (2023) · Cells · doi:10.3390/cells12060963 · Cited by 24
Pharmacotherapy for Co-Occurring Alcohol Use Disorder and Post-Traumatic Stress Disorder: Targeting the Opioidergic, Noradrenergic, Serotonergic, and GABAergic/Glutamatergic Systems
Verplaetse, T. L. (2018) · Alcohol research · doi:10.35946/arcr.v39.2.09 · Cited by 22
Quantification of alcohol drinking patterns in mice
Eisenhardt, M., Leixner, S., Spanagel, R., & Bilbao, A. (2015) · Addiction Biology · doi:10.1111/adb.12325 · Cited by 21
Self-citation
Calcium‐permeable AMPA receptor activity and GluA1 trafficking in the basolateral amygdala regulate operant alcohol self‐administration
Faccidomo, S., Cogan, E. S., Hon, O. J., Hoffman, J. L., Saunders, B. L., Eastman, V. R., Kim, M. J., Taylor, S. M., McElligott, Z. A., & Hodge, C. W. (2021) · Addiction Biology · doi:10.1111/adb.13049 · Cited by 21
Clinical Neuroscience of Addiction: Similarities and Differences Between Alcohol and Other Drugs
Karoly, H. C., YorkWilliams, S. L., & Hutchison, K. E. (2015) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12884 · Cited by 19
Dysregulated Glycine Signaling Contributes to Increased Impulsivity during Protracted Alcohol Abstinence
Irimia, C., Buczynski, M. W., Natividad, L. A., Laredo, S. A., Avalos, L. N., & Parsons, L. H. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2466-16.2017 · Cited by 19
Calcium chloride mimics the effects of acamprosate on cognitive deficits in chronic alcohol-exposed mice
Pradhan, G., Melugin, P. R., Wu, F., Fang, H. M., Weber, R. E., & Kroener, S. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4900-1 · Cited by 21
Inhibition of AMPA receptors (AMPARs) containing transmembrane AMPAR regulatory protein γ‐8 with JNJ‐55511118 shows preclinical efficacy in reducing chronic repetitive alcohol self‐administration
Hoffman, J. L., Faccidomo, S., Saunders, B. L., Taylor, S. M., Kim, M., & Hodge, C. W. (2021) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14639 · Cited by 16
Mechanisms underlying sleep–wake disturbances in alcoholism: Focus on the cholinergic pedunculopontine tegmentum
Knapp, C. M., Ciraulo, D. A., & Datta, S. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.029 · Cited by 19
Implication of Genes for the N-Methyl-d-Aspartate (NMDA) Receptor in Substance Addictions
Chen, J., Ma, Y., Fan, R., Yang, Z., & Li, M. D. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0877-3 · Cited by 18
Ceftriaxone Attenuated Anxiety-Like Behavior and Enhanced Brain Glutamate Transport in Zebrafish Subjected to Alcohol Withdrawal
Agostini, J. F., Costa, N. L. F., Bernardo, H. T., Baldin, S. L., Mendes, N. V., Pickler, K. D. P., Manenti, M. C., & Rico, E. P. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03008-z · Cited by 18
Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats
Kalejaiye, O., Getachew, B., Ferguson, C. L., Taylor, R. E., & Tizabi, Y. (2017) · Journal of Drug and Alcohol Research · doi:10.4303/jdar/236036 · Cited by 17
Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats
Getachew, B., & Tizabi, Y. (2018) · Journal of Drug and Alcohol Research · doi:10.4303/jdar/236069 · Cited by 17
Sobriety and Satiety: Is NAD+ the Answer?
Braidy, N., Villalva, M. D., & van Eeden, S. (2020) · Antioxidants · doi:10.3390/antiox9050425 · Cited by 17
The intermittent administration of ethanol during the juvenile period produces changes in the expression of hippocampal genes and proteins and deterioration of spatial memory
Contreras, A., Morales, L., & Olmo, N. D. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112033 · Cited by 17
Effect of ketamine on binge drinking patterns in crossed high alcohol-preferring (cHAP) mice
Ardinger, C. E., Winkler, G. A., Lapish, C. C., & Grahame, N. J. (2021) · Alcohol · doi:10.1016/j.alcohol.2021.09.004 · Cited by 16
Chronic Methylphenidate Alters Tonic and Phasic Glutamate Signaling in the Frontal Cortex of a Freely-Moving Rat Model of ADHD
Miller, E. M., Quintero, J. E., Pomerleau, F., Huettl, P. F., Gerhardt, G. A., & Glaser, P. E. A. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2483-1 · Cited by 16
Fish oil treatment reduces chronic alcohol exposure induced synaptic changes
Shi, Z., Xie, Y., Ren, H., He, B., Wang, M., Wan, J., Yuan, T., Yao, X., & Su, H. (2018) · Addiction Biology · doi:10.1111/adb.12623 · Cited by 18
Targeting Glycine Reuptake in Alcohol Seeking and Relapse
Vengeliene, V., Roßmanith, M., Takahashi, T. T., Alberati, D., Behl, B., Bespalov, A., & Spanagel, R. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.117.244822 · Cited by 16
Self-citation
Alcohol use and the pain system
Vigorito, M., & Chang, S. L. (2024) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2024.12005 · Cited by 15
Reduced ethanol drinking following selective cortical interneuron deletion of the GluN2B NMDA receptors subunit
Radke, A. K., Jury, N. J., Delpire, E. J., Nakazawa, K., & Holmes, A. (2016) · Alcohol · doi:10.1016/j.alcohol.2016.07.005 · Cited by 15
Self-citation
Changes in the serum metabolite profile correlate with decreased brain gray matter volume in moderate-to-heavy drinking young adults
Heikkinen, N., Kärkkäinen, O. K., Laukkanen, E., Kekkonen, V., Kaarre, O., Kivimäki, P., Könönen, M., Velagapudi, V., Nandania, J., Lehto, S. M., et al. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.05.010 · Cited by 15
Impaired discrimination learning in interneuronal NMDAR-GluN2B mutant mice
Brigman, J. L., Daut, R. A., Saksida, L. M., Bussey, T. J., Nakazawa, K., & Holmes, A. (2015) · Neuroreport · doi:10.1097/wnr.0000000000000373 · Cited by 15
Self-citation
Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders
Moaddab, M., Mangone, E., Ray, M. H., & McDannald, M. A. (2017) · Brain Sciences · doi:10.3390/brainsci7110151 · Cited by 14
Serum Metabolite Profile in Progressive Versus Nonprogressive Alcohol‐Related Liver Disease: A Cross‐Sectional Metabolomics Study
Puhakka, E., Ahmed, H., Haikonen, R., Leclercq, S., Hanhineva, K., Maccioni, L., Amadieu, C., Lehtonen, M., Männistö, V., Rysä, J., et al. (2025) · Liver International · doi:10.1111/liv.70128 · Cited by 14
mGlu2 mechanism-based interventions to treat alcohol relapse
Vengeliene, V., & Spanagel, R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.985954 · Cited by 14
Self-citation
Intersubunit interactions at putative sites of ethanol action in the M3 and M4 domains of the NMDA receptor GluN1 and GluN2B subunits
Zhao, Y., Ren, H., & Peoples, R. W. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13487 · Cited by 14
PPARα/CB1 receptor dual ligands as a novel therapy for alcohol use disorder: Evaluation of a novel oleic acid conjugate in preclinical rat models
Alén, F., Decara, J. M., Brunori, G., You, Z., Bühler, K., López‐Moreno, J. A., Cippitelli, A., Pavón, F. J., Suárez, J., Gardner, E. L., et al. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.008 · Cited by 14
No association of GSTP1 rs1695 polymorphism with amyotrophic lateral sclerosis: A case-control study in the Brazilian population
Barros, J. B. D. S., Santos, K. D. F., Azevedo, R. M., de Oliveira, R. P. D., Leobas, A. C. D., Bento, D. D. C. P., Santos, R. D. S., & Reis, Â. A. D. S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247024 · Cited by 14
Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial
Vanderijst, L., Hever, F., Buot, A., Dauré, C., Benoit, J., Hanak, C., Veeser, J., Morgiève, M., Campanella, S., Kornreich, C., et al. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05502-y · Cited by 13
COR758, a negative allosteric modulator of GABAB receptors
Porcu, A., Mostallino, R., Serra, V., Melis, M., Sogos, V., Beggiato, S., Ferraro, L., Manetti, F., Gianibbi, B., Bettler, B., et al. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108537 · Cited by 13
Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking
González‐Marín, M. C., Lebourgeois, S., Jeanblanc, J., Diouf, M., & Naassïla, M. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.07.015 · Cited by 16
Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer, A. T., Angarita, G. A., Esterlis, I., Anderson, J. M., Nabulsi, N., Lim, K., Ropchan, J. R., Carson, R. E., Krystal, J. H., Malley, S., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00856-9 · Cited by 13
Self-citation
Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor
Filarowska, J., Komsta, Ł., Smaga, I., Surówka, P., Marszałek‐Grabska, M., Grochecki, P., Nizio, D., Filip, M., & Kotlinska, J. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105350 · Cited by 13
Altered Relation Between Lipopolysaccharide‐Induced Inflammatory Response and Excitotoxicity in Rat Organotypic Hippocampal Slice Cultures During Ethanol Withdrawal
Lutz, J. A., Carter, M., Fields, L., Barron, S., & Littleton, J. M. (2015) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12705 · Cited by 12

Authors: Holmes, A., Spanagel, R., & Krystal, J. H.
Affiliations: National Institutes of Health (US)
Heidelberg University (DE)
Yale University (US)
Corresponding author: Holmes, Andrew
ORCID: Holmes, Andrew
Spanagel, Rainer
Krystal, John H.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2013-09-01
Volume: 229
Issue: 3
Pages: 539-554
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-013-3226-2
PMC: PMC3811052
OpenAlex: W2104412023
Cited by: 197
References: 221
Citations by year: 2026: 7 · 2025: 14 · 2024: 10 · 2023: 5 · 2022: 7 · 2021: 15 · 2020: 16 · 2019: 15 · 2018: 22 · 2017: 14 · 2016: 25 · 2015: 29 · 2014: 17 · 2013: 1
FWCI: 2.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (P50AA012870, ZIAAA000411)
National Center for Research Resources (UL1RR024139)
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: glutamatergic system, alcoholism, alcoholism pharmacotherapy, NMDA receptor, NMDA receptor glycine site, AMPA receptors, kainate receptors, metabotropic glutamate receptors, mGluR5, glutamate transporters, GluN2B, GluA3, alcohol withdrawal, alcohol craving, alcohol seeking, chronic ethanol exposure, glutamate excitotoxicity
MeSH terms: Alcoholism, Animals, Humans, Substance Withdrawal Syndrome, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Kainic Acid Receptors, Glutamic Acid, Protein Subunits, Molecular Targeted Therapy, Drug-Seeking Behavior

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Glutamatergic targets for new alcohol medications

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks