ArticleProceedings of the National Academy of Sciences of the United States of America2020
Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA-GABA transmission in highly addicted rats.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Genome-wide association study of cocaine self-administration behavior in Heterogeneous Stock rats.Nature communications · 2026Article
- Ivermectin reduces withdrawal-induced alcohol intake in rats: Association with CeA GABAergic enhancement and P2rx4 genetic liability.Neuropharmacology · 2026Article
- Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- High incidence of estrous cycle irregularities in heterogeneous stock (HS) rats is associated with footshock-resistant cocaine intake.Psychopharmacology · 2026Article
- The Therapeutic Potential of Dual NMR (NOP/MOP) Agonism in Pain Management.Pain and therapy · 2026Review
- Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts.European archives of psychiatry and clinical neuroscience · 2026Article
- Evaluating the reinforcing properties of oxycodone and oxymorphone using intravenous drug self-administration in male rats.Neuropharmacology · 2025Article
- Sex-specific transcriptional signatures of oxycodone persist during withdrawal and abstinence in the suprachiasmatic nucleus of heterogeneous stock rats.Addiction neuroscience · 2025Article
- Perinatal fentanyl exposure drives enduring addiction risk and central amygdala gene dysregulation.Neuropharmacology · 2025Article
- Crosstalk Between Glycinergic and N-Methyl-D-Aspartate Receptor-Mediated Glutamatergic Transmission in Behaviours Associated with Opioid Use Disorder.International journal of molecular sciences · 2025Review
- Automated pipeline for operant behavior phenotyping for high-throughput data management, processing, and visualization.NPP - digital psychiatry and neuroscience · 2025Article
- Ivermectin Reduces Withdrawal-Induced Alcohol Intake via CeA GABAergic Enhancement.bioRxiv : the preprint server for biology · 2025Article
- Impairment of the GABAergic system in the anterior midcingulate cortex of heroin-addicted males.European archives of psychiatry and clinical neuroscience · 2025Article
- Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors.Addiction neuroscience · 2025Article
- A Preclinical Alcohol Biobank: Samples from Behaviorally Characterized HS Rats for AUD Research.eNeuro · 2025Article
- Predicting individual treatment response in alcohol use disorders: a reverse translational proof-of-concept study.Translational psychiatry · 2025Article
- Calcium imaging of central amygdala activity after escalation of fentanyl self-administration.Neuropharmacology · 2025Article
- Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice.Psychopharmacology · 2025Article
- Impairment of the GABAergic system in the anterior insular cortex of heroin-addicted males.European archives of psychiatry and clinical neuroscience · 2025Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the amygdala (CeA), we found that rats with high addiction-like behaviors (HA) exhibited a significant increase in γ-aminobutyric acid (GABA) transmission compared with rats with low addiction-like behaviors (LA) and naive rats. The superfusion of CeA slices with nociceptin/orphanin FQ peptide (N/OFQ; 500 nM), an endogenous opioid-like peptide, normalized GABA transmission in HA rats. Intra-CeA levels of N/OFQ were lower in HA rats than in LA rats. Intra-CeA infusions of N/OFQ (1 μg per site) reversed the escalation of oxycodone self-administration in HA rats but not in LA rats. These results demonstrate that the downregulation of N/OFQ levels in the CeA may be responsible for hyper-GABAergic tone in the CeA that is observed in individuals who develop addiction-like behaviors. Based on these results, we hypothesize that small molecules that target the N/OFQ system might be useful for the treatment of opioid use disorder.
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Registered trials
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.