ArticleBiological psychiatry2016
Moderate Alcohol Drinking and the Amygdala Proteome: Identification and Validation of Calcium/Calmodulin Dependent Kinase II and AMPA Receptor Activity as Novel Molecular Mechanisms of the Positive Reinforcing Effects of Alcohol.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 86 citations in OpenAlex.
- 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
- Ketogenic Diet Promotes Reward Learning by Upregulating Hippocampal CAMK2A Expression and Activating Dopamine Synaptic Signaling.International journal of molecular sciences · 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
- Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice.Frontiers in behavioral neuroscience · 2025Article
- Biochemical changes precede affective and cognitive anomalies in aging adult C57BL/6J mice with a prior history of adolescent alcohol binge-drinking.Addiction biology · 2024Article
- Differential regulation of G protein-coupled receptor-associated proteins in the caudate and the putamen of cynomolgus macaques following chronic ethanol drinking.Journal of neurochemistry · 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
- Analysis of microRNAs and the microRNA-messengerRNA regulatory network in chronic alcohol exposure.Frontiers in pharmacology · 2024Article
- Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder.Addiction neuroscience · 2023Article
- LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Alcohol-drinking during later life by C57BL/6J mice induces sex- and age-dependent changes in hippocampal and prefrontal cortex expression of glutamate receptors and neuropathology markers.Addiction neuroscience · 2023Article
- 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
- A subchronic history of binge-drinking elicits mild, age- and sex-selective, affective, and cognitive anomalies in C57BL/6J mice.Frontiers in behavioral neuroscience · 2023Article
- Alcohol-Drinking Under Limited-Access Procedures During Mature Adulthood Accelerates the Onset of Cognitive Impairment in Mice.Frontiers in behavioral neuroscience · 2022Article
- Sex-specific plasticity in CRF regulation of inhibitory control in central amygdala CRF1 neurons after chronic voluntary alcohol drinking.Addiction biology · 2022Article
- Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression.Frontiers in behavioral neuroscience · 2022Article
- Reduced exploratory behavior in neuronal nucleoredoxin knockout mice.Redox biology · 2021Article
- Calcium-permeable AMPA receptor activity and GluA1 trafficking in the basolateral amygdala regulate operant alcohol self-administration.Addiction biology · 2021Article
- Alcohol dependence activates ventral tegmental area projections to central amygdala in male mice and rats.Addiction biology · 2021Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDespite worldwide consumption of moderate amounts of alcohol, the neural mechanisms that mediate the transition from use to abuse are not fully understood.
methodsHere, we conducted a high-throughput screen of the amygdala proteome in mice after moderate alcohol drinking (n = 12/group) followed by behavioral studies (n = 6-8/group) to uncover novel molecular mechanisms of the positive reinforcing properties of alcohol that strongly influence the development of addiction.
resultsTwo-dimensional difference in-gel electrophoresis with matrix assisted laser desorption ionization tandem time-of-flight identified 29 differentially expressed proteins in the amygdala of nondependent C57BL/6J mice following 24 days of alcohol drinking. Alcohol-sensitive proteins included calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) and a network of functionally linked proteins that regulate neural plasticity and glutamate-mediated synaptic activity. Accordingly, alcohol drinking increased α-amino-3-hydroxy-5-methyl-4-isooxazole receptor (AMPAR) in central amygdala (CeA) and phosphorylation of AMPAR GluA1 subunit at a CaMKII locus (GluA1-Ser831) in CeA and lateral amygdala. Further, CaMKIIα-Thr286 and GluA1-Ser831 phosphorylation was increased in CeA and lateral amygdala of mice that lever-pressed for alcohol versus the nondrug reinforcer sucrose. Mechanistic studies showed that targeted pharmacologic inhibition of amygdala CaMKII or AMPAR activity specifically inhibited the positive reinforcing properties of alcohol but not sucrose.
conclusionsModerate alcohol drinking increases the activity and function of plasticity-linked protein networks in the amygdala that regulate the positive reinforcing effects of the drug. Given the prominence of positive reinforcement in the etiology of addiction, we propose that alcohol-induced adaptations in CaMKIIα and AMPAR signaling in the amygdala may serve as a molecular gateway from use to abuse.
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