ArticleAddiction biology2021
Calcium-permeable AMPA receptor activity and GluA1 trafficking in the basolateral amygdala regulate operant alcohol self-administration.
Article in Addiction biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 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
- AlteredeNeuro · 2026Article
- Transmembrane AMPA receptor regulatory protein TARP ɣ-8 is a target of ethanol that regulates self-administration and relapse in mice.Psychopharmacology · 2026Article
- INTERFERON-REGULATORY FACTOR 7: A NEUROIMMUNE ROLE FOR VAPOR-INDUCED ESCALATIONS IN ETHANOL SELF-ADMINISTRATION.bioRxiv : the preprint server for biology · 2026Article
- Glutamate delta-1 receptors regulate a tonic excitatory conductance in the mouse bed nucleus of the stria terminalis and influence neuronal function.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
- Suppression of mPFC-Amygdala Circuit Mitigates Sevoflurane-Induced Cognitive Deficits in Aged Mice.CNS neuroscience & therapeutics · 2025Article
- Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Oral fentanyl consumption and withdrawal impairs fear extinction learning and enhances basolateral amygdala principal neuron excitatory-inhibitory balance in male and female mice.Addiction neuroscience · 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
- Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder.Addiction neuroscience · 2023Article
- Insula Dynorphin and Kappa Opioid Receptor Systems Regulate Alcohol Drinking in a Sex-Specific Manner in Mice.The Journal of neuroscience : the official journal of the Society for 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
- Preventing incubation of drug craving to treat drug relapse: from bench to bedside.Molecular psychiatry · 2023Review
- Tauopathy and alcohol consumption interact to alter locus coeruleus excitatory transmission and excitability in male and female mice.Alcohol (Fayetteville, N.Y.) · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Addiction is viewed as maladaptive glutamate-mediated neuroplasticity that is regulated, in part, by calcium-permeable AMPA receptor (CP-AMPAR) activity. However, the contribution of CP-AMPARs to alcohol-seeking behavior remains to be elucidated. We evaluated CP-AMPAR activity in the basolateral amygdala (BLA) as a potential target of alcohol that also regulates alcohol self-administration in C57BL/6J mice. Operant self-administration of sweetened alcohol increased spontaneous EPSC frequency in BLA neurons that project to the nucleus accumbens as compared with behavior-matched sucrose controls indicating an alcohol-specific upregulation of synaptic activity. Bath application of the CP-AMPAR antagonist NASPM decreased evoked EPSC amplitude only in alcohol self-administering mice indicating alcohol-induced synaptic insertion of CP-AMPARs in BLA projection neurons. Moreover, NASPM infusion in the BLA dose-dependently decreased the rate of operant alcohol self-administration providing direct evidence for CP-AMPAR regulation of alcohol reinforcement. As most CP-AMPARs are GluA1-containing, we asked if alcohol alters the activation state of GluA1-containing AMPARs. Immunocytochemistry results showed elevated GluA1-S831 phosphorylation in the BLA of alcohol as compared with sucrose mice. To investigate mechanistic regulation of alcohol self-administration by GluA1-containing AMPARs, we evaluated the necessity of GluA1 trafficking using a TET-ON AAV encoding a dominant-negative GluA1 c-terminus (GluA1ct) that blocks activity-dependent synaptic delivery of native GluA1-containing AMPARs. GluA1ct expression in the BLA reduced alcohol self-administration with no effect on sucrose controls. These results show that CP-AMPAR activity and GluA1 trafficking in the BLA mechanistically regulate the reinforcing effects of sweetened alcohol. Pharmacotherapeutic targeting these mechanisms of maladaptive neuroplasticity may aid medical management of alcohol use disorder.
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