ArticleAlcoholism, clinical and experimental research2021
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.
Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 16 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
- JNJ-55511118 Stabilizes a Desensitized-like Conformation of γ8-Containing AMPA Receptors through Long-Range Allosteric Modulation.bioRxiv : the preprint server for biology · 2025Article
- 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
- AMPA/kainate receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving.Frontiers in psychiatry · 2025Article
- 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
- Roles of AMPA receptors in social behaviors.Frontiers in synaptic neuroscience · 2024Review
- Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder.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
- Small-animal PET study for noninvasive quantification of transmembrane AMPA receptor regulatory proteinJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Shortening time for access to alcohol drives up front-loading behavior, bringing consumption in male rats to the level of females.Biology of sex differences · 2021Article
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6 authors at 1 institution in 1 country.
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Abstract
backgroundA prominent therapeutic indication for alcohol use disorder (AUD) is reduction in chronic repetitive alcohol use. Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) regulate chronic alcohol self-administration in preclinical models. Recent evidence indicates that the expression and function of AMPARs require the transmembrane AMPAR regulatory protein γ-8 (TARP γ-8). This study evaluated the preclinical efficacy of JNJ-55511118, a novel, selective, high-affinity inhibitor of TARP γ-8-bound AMPARs, in reducing chronic operant alcohol self-administration.
methodsSeparate groups of male and female C57BL/6J mice (n = 8/sex/group) were trained to lever press for sweetened alcohol (9% v/v + sucrose 2% w/v) or sucrose only (2% w/v) in operant conditioning chambers using an FR-4 schedule of reinforcement. After a 40-day baseline, JNJ-55511118 (0, 1, and 10 mg/kg, p.o.) was administered in randomized order 1 h before self-administration sessions. Parameters of operant behavior including response rate, total reinforcers, and head entries in the drinking troughs were computer recorded.
resultsDuring baseline, responding to alcohol, but not sucrose, was greater in female than male mice. In male mice, both doses of JNJ-55511118 decreased multiple parameters of alcohol self-administration but did not reduce behavior-matched sucrose-only self-administration. JNJ-55511118 had no effect on sweetened alcohol or sucrose self-administration in female mice. Subsequent tests of motor function showed that the lowest effective dose of JNJ-55511118 (1 mg/kg) had no effect on open-field activity in male mice.
conclusionsThis study shows for the first time that TARP γ-8-bound AMPARs regulate a behavioral pathology associated with addiction. The preclinical efficacy of JNJ-55511118 in reducing alcohol self-administration in male mice suggests that inhibition of TARP γ-8-bound AMPARs is a novel and highly significant neural target for developing medications to treat AUD and other forms of addiction.
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