The role of the NMDA receptor in alcohol relapse: a pharmacological mapping study using the alcohol deprivation effect.
paper
Cited
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- Authors
- Vengeliene, Valentina; Bachteler, Daniel; Danysz, Wojciech; Spanagel, Rainer
- Year
- 2005
- Journal
- Neuropharmacology
- PMID
- 15829254
- DOI
- 10.1016/j.neuropharm.2005.01.002
Modulators of glutamate receptors especially of the N-methyl-D-aspartate receptors (NMDARs) have recently been suggested as putative pharmacotherapeutic agents in the treatment of alcohol relapse. However, at present it is not clear, which binding and modulatory sites of the NMDAR are involved in relapse behavior. We, therefore, performed a pharmacological mapping study in long-term alcohol drinking rats using the alcohol deprivation effect (ADE) as a model for relapse behavior. In a comprehensive fashion, we studied dose-response curves, employing the following selective pharmacological agents: the NMDAR competitive antagonist CGP37849, the glycine binding site antagonist L-701.324, the NR2B subunit selective antagonist ifenprodil, which acts at the polyamine binding site, the NMDAR channel blocker neramexane, and ethanol, which acts as a functional antagonist at the NMDAR. Our data show that the animals' alcohol consumption inversely correlates with the dose of ethanol administered intraperitoneally. This indicates that under the present experimental conditions alcohol intake during an ADE is an entirely pharmacologically driven behavior that is not under the control of other factors such as taste or novelty of alcohol re-exposure. The effects of the administration of the aforementioned compounds were comparable to those of ethanol, suggesting a similar pharmacological impact on relapse behavior. Repeated administration of both competitive and uncompetitive NMDAR antagonist dose-dependently suppressed alcohol consumption during ADE. In addition, ifenprodil and L-701.324 dose-dependently reduced the expression of an ADE as well. In summary, the results suggest that an inhibition of NMDAR function in general, rather than a particular interference with a specific binding site of this receptor, is sufficient for the reduction of relapse behavior.
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
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| A new module in the drug development process: preclinical multi-center randomized controlled trial of R-ketamine on alcohol relapse. | Meinhardt MW et al. | โ | 2025 | โ |
| Evaluation of glycine treatment for reducing alcohol craving and self-administration in individuals with alcohol use disorder: A human laboratory trial. | Olsson Y et al. | โ | 2025 | โ |
| Sex-associated differences in incentive salience and drinking behaviour in a rodent model of alcohol relapse. | Hakus A et al. | โ | 2025 | โ |
| The Continuing Challenges of Studying Parallel Behaviours in Humans and Animal Models. | Crombag HS et al. | โ | 2025 | โ |
| Dissecting operant alcohol self-administration using saccharin-fading procedure. | Calleja-Conde J et al. | โ | 2023 | โ |
| GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential. | Dharavath RN et al. | โ | 2023 | โ |
| N-Acetylcysteine normalizes brain oxidative stress and neuroinflammation observed after protracted ethanol abstinence: a preclinical study in long-term ethanol-experienced male rats. | Fernรกndez-Rodrรญguez S et al. | โ | 2023 | โ |
| Different brain oxidative and neuroinflammation status in rats during prolonged abstinence depending on their ethanol relapse-like drinking behavior: Effects of ethanol reintroduction. | Fernรกndez-Rodrรญguez S et al. | โ | 2022 | โ |
| FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION. | Bowen MT et al. | โ | 2022 | โ |
| Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor. | Filarowska-Jurko J et al. | โ | 2022 | โ |
| Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review. | Fischler PV et al. | โ | 2022 | โ |
| Effects of systemic glycine on accumbal glycine and dopamine levels and ethanol intake in male Wistar rats. | Olsson Y et al. | โ | 2021 | โ |
| Efficacy of N-acetylcysteine in the prevention of alcohol relapse-like drinking: Study in long-term ethanol-experienced male rats. | Cano-Cebriรกn MJ et al. | โ | 2021 | โ |
| Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation? | Borruto AM et al. | โ | 2021 | โ |
| Neurobiology of alcohol seeking behavior. | Domi E et al. | โ | 2021 | โ |
| NMDA Receptors in Accumbal D1 Neurons Influence Chronic Sugar Consumption and Relapse. | Wei S et al. | โ | 2021 | โ |
| Effects of Cocaine Exposure on Astrocytic Glutamate Transporters and Relapse-Like Ethanol-Drinking Behavior in Male Alcohol-Preferring Rats. | Hammad AM et al. | โ | 2020 | โ |
| Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse. | Meinhardt MW et al. | โ | 2020 | โ |
| Both ketamine and NBQX attenuate alcohol drinking in male Wistar rats. | Ruda-Kucerova J et al. | โ | 2018 | โ |
| Commonality of Ethanol and Nicotine Reinforcement and Relapse in Wistar-Derived UChB Rats: Inhibition by N-Acetylcysteine. | Quintanilla ME et al. | โ | 2018 | โ |
| Effects of alcohol and psychostimulants on the vasopressin system: behavioral implications. | Godino A et al. | โ | 2018 | โ |
| Implication of Genes for the N-Methyl-D-Aspartate (NMDA) Receptor in Substance Addictions. | Chen J et al. | โ | 2018 | โ |
| Targeting Glycine Reuptake in Alcohol Seeking and Relapse. | Vengeliene V et al. | โ | 2018 | โ |
| Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line. | Israel Y et al. | โ | 2017 | โ |
| Do specific NMDA receptor subunits act as gateways for addictive behaviors? | Hopf FW | โ | 2017 | โ |
| Dysregulated Glycine Signaling Contributes to Increased Impulsivity during Protracted Alcohol Abstinence. | Irimia C et al. | โ | 2017 | โ |
| Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective | Hwa L et al. | โ | 2017 | โ |
| Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective. | Hwa L et al. | โ | 2017 | โ |
| Induction and Blockade of Adolescent Cocaine-Induced Habits. | DePoy LM et al. | โ | 2017 | โ |
| Rat animal models for screening medications to treat alcohol use disorders. | Bell RL et al. | โ | 2017 | โ |
| Reduced ethanol drinking following selective cortical interneuron deletion of the GluN2B NMDA receptors subunit. | Radke AK et al. | โ | 2017 | โ |
| Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression. | Camarini R et al. | โ | 2016 | โ |
| Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse. | Vengeliene V et al. | โ | 2016 | โ |
| The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile. | Vengeliene V et al. | โ | 2016 | โ |
| Cortical GluN2B deletion attenuates punished suppression of food reward-seeking. | Radke AK et al. | โ | 2015 | โ |
| Different sites of alcohol action in the NMDA receptor GluN2A and GluN2B subunits. | Zhao Y et al. | โ | 2015 | โ |
| Glutamate Receptors within the Mesolimbic Dopamine System Mediate Alcohol Relapse Behavior. | Eisenhardt M et al. | โ | 2015 | โ |
| Long-lasting effect of NMDA receptor antagonist memantine on ethanol-cue association and relapse. | Vengeliene V et al. | โ | 2015 | โ |
| Long-term inhibition of ethanol intake by the administration of an aldehyde dehydrogenase-2 (ALDH2)-coding lentiviral vector into the ventral tegmental area of rats. | Karahanian E et al. | โ | 2015 | โ |
| N-methyl-D-aspartate receptor antagonism has differential effects on alcohol craving and drinking in heavy drinkers. | Krishnan-Sarin S et al. | โ | 2015 | โ |
| Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following Psychostimulant Exposure. | DePoy LM et al. | โ | 2015 | โ |
| The "first hit" toward alcohol reinforcement: role of ethanol metabolites. | Israel Y et al. | โ | 2015 | โ |
| Circadian rhythms and addiction: mechanistic insights and future directions. | Logan RW et al. | โ | 2014 | โ |
| Convergent pharmacological mechanisms in impulsivity and addiction: insights from rodent models. | Jupp B et al. | โ | 2014 | โ |
| Co-occurring psychiatric disorders and alcoholism. | Stephen Rich J et al. | โ | 2014 | โ |
| Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats. | Orrico A et al. | โ | 2014 | โ |
| Ethanol pre-exposure during adolescence or adulthood increases ethanol intake but ethanol-induced conditioned place preference is enhanced only when pre-exposure occurs in adolescence. | Carrara-Nascimento PF et al. | โ | 2014 | โ |
| [Pharmacological profiles and clinical roles of acamprosate (Regtect(ยฎ) tablets 333 mg) for the maintenance of abstinence in alcohol-dependent patients]. | Ohhara T et al. | โ | 2014 | โ |
| Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics. | Jin Z et al. | โ | 2014 | โ |
| The effects of xenon and nitrous oxide gases on alcohol relapse. | Vengeliene V et al. | โ | 2014 | โ |
| Acamprosate {monocalcium bis(3-acetamidopropane-1-sulfonate)} reduces ethanol-drinking behavior in rats and glutamate-induced toxicity in ethanol-exposed primary rat cortical neuronal cultures. | Oka M et al. | โ | 2013 | โ |
| A systems medicine research approach for studying alcohol addiction. | Spanagel R et al. | โ | 2013 | โ |
| Ceftriaxone, a beta-lactam antibiotic, attenuates relapse-like ethanol-drinking behavior in alcohol-preferring rats. | Qrunfleh AM et al. | โ | 2013 | โ |
| Efficacy of D-penicillamine, a sequestering acetaldehyde agent, in the prevention of alcohol relapse-like drinking in rats. | Orrico A et al. | โ | 2013 | โ |
| Glutamatergic targets for new alcohol medications. | Holmes A et al. | โ | 2013 | โ |
| Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain. | Harvey RJ et al. | โ | 2013 | โ |
| Neurobiology of an endophenotype: modeling the progression of alcohol addiction in rodents. | Mahoney MK et al. | โ | 2013 | โ |
| Probing the modulation of acute ethanol intoxication by pharmacological manipulation of the NMDAR glycine co-agonist site. | Debrouse L et al. | โ | 2013 | โ |
| The alcohol deprivation effect: marked inhibition by anticatalase gene administration into the ventral tegmental area in rats. | Tampier L et al. | โ | 2013 | โ |
| Adenosine and glutamate signaling in neuron-glial interactions: implications in alcoholism and sleep disorders. | Nam HW et al. | โ | 2012 | โ |
| Glucocorticoid and polyamine interactions in the plasticity of glutamatergic synapses that contribute to ethanol-associated dependence and neuronal injury. | Prendergast MA et al. | โ | 2012 | โ |
| Heterozygous deletion of NR1 subunit of the NMDA receptor alters ethanol-related behaviors and regional expression of NR2 subunits in the brain. | Du X et al. | โ | 2012 | โ |
| Inhibition of the casein-kinase-1-ฮต/ฮด/ prevents relapse-like alcohol drinking. | Perreau-Lenz S et al. | โ | 2012 | โ |
| Polyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependence. | Barron S et al. | โ | 2012 | โ |
| The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in the rat; tolerance development to acamprosate but not to Org24598. | Lidรถ HH et al. | โ | 2012 | โ |
| Timing-dependent reduction in ethanol sedation and drinking preference by NMDA receptor co-agonist d-serine. | Lockridge A et al. | โ | 2012 | โ |
| A role for accumbal glycine receptors in modulation of dopamine release by the glycine transporter-1 inhibitor org25935. | Lidรถ HH et al. | โ | 2011 | โ |
| Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates. | Cuzon Carlson VC et al. | โ | 2011 | โ |
| Type 1 equilibrative nucleoside transporter regulates ethanol drinking through accumbal N-methyl-D-aspartate receptor signaling. | Nam HW et al. | โ | 2011 | โ |
| An integrated genome research network for studying the genetics of alcohol addiction. | Spanagel R et al. | โ | 2010 | โ |
| Genetic research: who is at risk for alcoholism. | Foroud T et al. | โ | 2010 | โ |
| Glycine transporter-1 blockade leads to persistently reduced relapse-like alcohol drinking in rats. | Vengeliene V et al. | โ | 2010 | โ |
| Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism. | Li Z et al. | โ | 2010 | โ |
| Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse. | Wang J et al. | โ | 2010 | โ |
| Alcoholism: a systems approach from molecular physiology to addictive behavior. | Spanagel R | โ | 2009 | โ |
| A short review on the aetiology and pathophysiology of alcoholism. | Moussas G et al. | โ | 2009 | โ |
| Compulsive alcohol drinking in rodents. | Vengeliene V et al. | โ | 2009 | โ |
| Different effects of two N-methyl-D-aspartate receptor antagonists on seizures, spontaneous behavior, and motor performance in immature rats. | Mares P et al. | โ | 2009 | โ |
| Neramexane: a moderate-affinity NMDA receptor channel blocker: new prospects and indications. | Rammes G | โ | 2009 | โ |
| Oral glycine administration increases brain glycine/creatine ratios in men: a proton magnetic resonance spectroscopy study. | Kaufman MJ et al. | โ | 2009 | โ |
| The alcohol deprivation effect in C57BL/6J mice is observed using operant self-administration procedures and is modulated by CRF-1 receptor signaling. | Sparta DR et al. | โ | 2009 | โ |
| The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens. | Lidรถ HH et al. | โ | 2009 | โ |
| Absence of significant interactive effects of high-dose D-cycloserine and ethanol in healthy human subjects: preliminary insights into ethanol actions at the glycine B site of NMDA glutamate receptors. | Trevisan L et al. | โ | 2008 | โ |
| Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice. | Farook JM et al. | โ | 2008 | โ |
| Alcohol preference in mice lacking the Avpr1a vasopressin receptor. | Sanbe A et al. | โ | 2008 | โ |
| Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats. | Adams CL et al. | โ | 2008 | โ |
| Drugs for relapse prevention of alcoholism: ten years of progress. | Spanagel R et al. | โ | 2008 | โ |
| Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats. | Toalston JE et al. | โ | 2008 | โ |
| Effects of mGlu1-receptor blockade on ethanol self-administration in inbred alcohol-preferring rats. | Besheer J et al. | โ | 2008 | โ |
| Glutamatergic substrates of drug addiction and alcoholism. | Gass JT et al. | โ | 2008 | โ |
| How adaptation of the brain to alcohol leads to dependence: a pharmacological perspective. | Clapp P et al. | โ | 2008 | โ |
| Injection of the neuropeptide CNP into dopaminergic rat brain areas decreases alcohol intake. | Romieu P et al. | โ | 2008 | โ |
| Metabotropic glutamate 5 receptors regulate sensitivity to ethanol in mice. | Bird MK et al. | โ | 2008 | โ |
| Neuropharmacology of alcohol addiction. | Vengeliene V et al. | โ | 2008 | โ |
| Adolescence, glucocorticoids and alcohol. | Prendergast MA et al. | โ | 2007 | โ |
| The CB1 cannabinoid receptor antagonist rimonabant chronically prevents the nicotine-induced relapse to alcohol. | Lรณpez-Moreno JA et al. | โ | 2007 | โ |
| The effects of lamotrigine on alcohol seeking and relapse. | Vengeliene V et al. | โ | 2007 | โ |
| The role of protein kinase A in acute ethanol-induced neurobehavioral actions in rats. | Lai CC et al. | โ | 2007 | โ |
| Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: an animal model to study the neurobiology of alcoholism. | Ciccocioppo R et al. | โ | 2006 | โ |
| Involvement of the AMPA receptor GluR-C subunit in alcohol-seeking behavior and relapse. | Sanchis-Segura C et al. | โ | 2006 | โ |
| The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse. | Vengeliene V et al. | โ | 2006 | โ |
| The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. | Hodge CW et al. | โ | 2006 | โ |
| Withdrawal from free-choice ethanol consumption results in increased packing density of glutamine synthetase-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. | Miguel-Hidalgo JJ | โ | 2006 | โ |
| Role of altered structure and function of NMDA receptors in development of alcohol dependence. | Nagy J et al. | โ | 2005 | โ |