ArticlePsychopharmacology2018
Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.
Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Genetic influences on alcohol flushing in East Asian populations.BMC genomics · 2023Pooled it
- Ethanol Self-Administration Reduces mGlu2/3 Protein Expression in the Nucleus Accumbens and mGlu2/3 Activation Suppresses Binge Drinking in Male Mice.Alcohol, clinical & experimental research · 2026Article
- Transmembrane AMPA receptor regulatory protein TARP ɣ-8 is a target of ethanol that regulates self-administration and relapse in mice.Psychopharmacology · 2026Article
- Ethanol self-administration targets GluA2-containing AMPA receptor expression and synaptic activity in the nucleus accumbens in a manner that drives the positive reinforcing properties of the drug.Psychopharmacology · 2025Article
- Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Distinct sex differences in ethanol consumption and operant self-administration in C57BL/6J mice with uniform regulation by glutamate AMPAR activity.Frontiers in behavioral neuroscience · 2024Article
- Negative modulation of AMPA receptors bound to transmembrane AMPA receptor regulatory protein γ-8 blunts the positive reinforcing properties of alcohol and sucrose in a brain region-dependent manner in male mice.Psychopharmacology · 2023Article
- Neuropharmacology of Alcohol Addiction with Special Emphasis on Proteomic Approaches for Identification of Novel Therapeutic Targets.Current neuropharmacology · 2023Article
- Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the nucleus accumbens in mice.Psychopharmacology · 2022Article
- 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.Alcoholism, clinical and experimental research · 2021Article
- Pharmacological inhibition of glycogen synthase kinase 3 increases operant alcohol self-administration in a manner associated with altered pGSK-3β, protein interacting with C kinase and GluA2 protein expression in the reward pathway of male C57BL/6J mice.Behavioural pharmacology · 2020Article
- Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease.International review of neurobiology · 2019Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThere is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking.
objectiveThe goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development. MATERIALS AND
methodsTwo-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose.
resultsExpression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30 mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a manner associated with nonspecific motor inhibition.
conclusionsProtein expression profiling identified an array of proteins and networks in the NAcb, including GSTP1, that are novel molecular targets of chronic alcohol drinking. Pharmacological inhibition of GSTP1 significantly reduced the positive reinforcing effects of alcohol, which regulate repetitive use and abuse liability. The observation that this protein was both upregulated after chronic drinking and that its inhibition could modulate the reinforcing properties of alcohol suggests that it is a key target for alcohol-related pathologies. Proteomic strategies combined with specific preclinical models has potential to identify and validate novel targets of alcohol that may be useful in the medical management of alcohol addiction.
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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.