ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 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, 19 citations in OpenAlex.
- Systemic Everolimus Does Not Block the Incubation of Methamphetamine-Craving: A Dose-Response Study.Addiction biology · 2026Article
- Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Chronic delivery of buprenorphine during abstinence decreases incubation of heroin seeking and neuronal activation in medial prefrontal cortex and striatum in male and female rats.Psychopharmacology · 2025Article
- Biomolecular correlates of incubated sucrose-seeking within ventromedial prefrontal cortex are sex- and subregion-selective.Pharmacology, biochemistry, and behavior · 2025Article
- AMPA receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving.bioRxiv : the preprint server for biology · 2025Article
- Neurobiology of the incubation of drug craving: An update.Pharmacological reviews · 2025Review
- AMPA/kainate receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving.Frontiers in psychiatry · 2025Article
- Replication and extension of the subregion selectivity of glutamate-related changes within the nucleus accumbens associated with the incubation of cocaine-craving.Pharmacology, biochemistry, and behavior · 2024Article
- 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
- KAddiction biology · 2024Article
- Neuropharmacological Evidence Implicating Drug-Induced Glutamate Receptor Dysfunction in Affective and Cognitive Sequelae of Subchronic Methamphetamine Self-Administration in Mice.International journal of molecular sciences · 2024Article
- Subunit-selective PI3-kinase control of action strategies in the medial prefrontal cortex.Neurobiology of learning and memory · 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
- Preventing incubation of drug craving to treat drug relapse: from bench to bedside.Molecular psychiatry · 2023Review
- Profiling prefrontal cortex protein expression in rats exhibiting an incubation of cocaine craving following short-access self-administration procedures.Frontiers in psychiatry · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Cue-elicited drug-craving is a cardinal feature of addiction that intensifies (incubates) during protracted withdrawal. In a rat model, these addiction-related behavioral pathologies are mediated, respectively, by time-dependent increases in PI3K/Akt1 signaling and reduced Group 1 metabotropic glutamate receptor (mGlu) expression, within the ventromedial prefrontal cortex (vmPFC). Herein, we examined the capacity of single oral dosing with everolimus, an FDA-approved inhibitor of the PI3K/Akt effector mTOR, to reduce incubated cocaine-craving and reverse incubation-associated changes in vmPFC kinase activity and mGlu expression. Rats were trained to lever-press for intravenous infusions of cocaine or delivery of sucrose pellets and then subjected to tests for cue-reinforced responding during early (3 days) or late (30-46 days) withdrawal. Rats were gavage-infused with everolimus (0-1.0 mg/kg), either prior to testing to examine for effects upon reinforcer-seeking behavior, or immediately following testing to probe effects upon the consolidation of extinction learning. Single oral dosing with everolimus dose-dependently blocked cocaine-seeking during late withdrawal and the effect lasted at least 24 h. No everolimus effects were observed for cue-elicited sucrose-seeking or cocaine-seeking in early withdrawal. In addition, everolimus treatment, following initial cue-testing, reduced subsequent cue hyper-responsivity exhibited observed during late withdrawal, arguing a facilitation of extinction memory consolidation. everolimus' "anti-incubation" effect was associated with a reversal of withdrawal-induced changes in indices of PI3K/Akt1/mTOR activity, as well as Homer protein and mGlu1/5 expression, within the prelimbic (PL) subregion of the prefrontal cortex. Our results indicate mTOR inhibition as a viable strategy for interrupting heightened cocaine-craving and facilitating addiction recovery during protracted withdrawal.
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