ArticleBiological psychiatry2014
The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 146 citations in OpenAlex.
- BLA kappa opioid receptor inputs to the BNST mediate social stress-induced increases in alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Review
- Dynorphinergic neuroadaptations in the islands of Calleja: implications for alcohol use disorder.bioRxiv : the preprint server for biology · 2026Article
- Proteomic analysis of central amygdala systems regulated by mifepristone in the context of alcohol dependence.Neuropharmacology · 2026Article
- Kappa opioid receptor control of motivated behavior revisited.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Expression of Dynorphin and Kappa-Opioid Receptors in the Bed Nucleus of the Stria Terminalis: Focus on Adolescent Development.International journal of molecular sciences · 2025Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- BLAbioRxiv : the preprint server for biology · 2024Article
- Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.Pharmacology, biochemistry, and behavior · 2024Article
- Acute and chronic alcohol modulation of extended amygdala calcium dynamics.Alcohol (Fayetteville, N.Y.) · 2024Article
- Nalmefene Hydrochloride: Potential Implications for Treating Alcohol and Opioid Use Disorder.Substance abuse and rehabilitation · 2024Review
- Brain proteomic atlas of alcohol use disorder in adult males.Translational psychiatry · 2023Article
- Acute and chronic alcohol modulation of extended amygdala calcium dynamics.bioRxiv : the preprint server for biology · 2023Article
- A critical review of effects on ethanol intake of the dynorphin/kappa opioid receptor system in the extended amygdala: From inhibition to stimulation.Alcohol, clinical & experimental research · 2023Review
- Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats.Neuropharmacology · 2023Article
- Dynorphin/Kappa Opioid Receptor Activity Within the Extended Amygdala Contributes to Stress-Enhanced Alcohol Drinking in Mice.Biological psychiatry · 2022Article
- Kappa-opioid receptor activation reinstates nicotine self-administration in mice.Addiction neuroscience · 2022Article
- Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.Pharmacology, biochemistry, and behavior · 2022Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations.
methodsMale Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor or air exposure. Changes in self-administration were assessed by pharmacologic challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [(35)S]GTPγS coupling assays were performed to assess KOR function.
resultsAlcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity, and KOR signaling in the amygdala compared with nondependent control rats. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats, whereas a mu-opioid receptor/delta-opioid receptor antagonist cocktail selectively reduced self-administration in nondependent rats. A mu-opioid receptor antagonist/partial KOR agonist attenuated self-administration in both cohorts.
conclusionsIncreased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.
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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.