The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats
Open accessAbstract
Previously, it was shown that ethanol-dependent animals display increased sensitivity to the general opioid receptor antagonist nalmefene compared to naltrexone. It was hypothesized that the dissociable effects of the two antagonists were attributable to a κ-opioid receptor mechanism. Nucleus accumbens dynorphin is upregulated following chronic ethanol exposure and such neuroadaptations could contribute to nalmefene's increased potency in ethanol-dependent animals. To test this hypothesis, male Wistar rats were trained to self-administer ethanol using an operant conditioning procedure. Animals were then implanted with bilateral intra-accumbens shell guide cannulae and assigned to either a chronic intermittent ethanol vapor-exposure condition (to induce dependence) or an air-exposed control group. Following a one-month exposure period, nalmefene, nor-binaltorphimine (nor-BNI; selective for κ-opioid receptors) or a combination of the selective opioid receptor antagonists CTOP and naltrindole (selective for the μ- and δ-opioid receptors, respectively) were site-specifically infused into the nucleus accumbens shell prior to ethanol self-administration sessions during acute withdrawal. Nalmefene and CTOP/naltrindole dose-dependently reduced ethanol self-administration in nondependent and dependent animals, whereas nor-BNI selectively attenuated ethanol self-administration in ethanol-dependent animals without affecting the self-administration of nondependent animals. Further analysis indentified that intra-accumbens shell nalmefene was more potent in ethanol-dependent animals and that the increased potency was attributable to a κ-opioid receptor mechanism. These data support the concept that dysregulation of DYN/κ-opioid receptor systems contributes to the excessive self-administration observed in dependent animals and suggest that pharmacotherapeutics for ethanol dependence that target κ-opioid receptors, in addition to μ- and δ-opioid receptors, are preferable to those that target μ- and δ-opioid receptor mechanisms alone.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These effects may be mediated by the extended amygdala, including the CeA and shell of the NAc (Nealey et al., 2011).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Nealey et al., 2011
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199
Actual Causes of Death in the United States, 2000
Mokdad, A. H. (2004) · JAMA · doi:10.1001/jama.291.10.1238 · Cited by 5,211
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733
The 1996 Guide for the Care and Use of Laboratory Animals
Clark, J. D., Gebhart, G. F., Gonder, J. C., Keeling, M. E., & Kohn, D. F. (1997) · ILAR Journal · doi:10.1093/ilar.38.1.41 · Cited by 4,429
The mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059
Naltrexone in the Treatment of Alcohol Dependence
Volpicelli, J. R. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820110040006 · Cited by 1,828
Grant, B. F., Dawson, D. A., Stinson, F. S., Chou, S. P., Dufour, M. C., & Pickering, R. P. (2004) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2004.02.004 · Cited by 1,509
Dopamine and drug addiction: the nucleus accumbens shell connection
Di Chiara, G., Bassareo, V., Fenu, S., De Luca, M. A., Spina, L., Cadoni, C., Acquas, E., Carboni, E., Valentini, V., & Lecca, D. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.06.032 · Cited by 935
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–132 of 132
Regulation of alcohol drinking by ventral striatum and extended amygdala circuitry
Borrego, M. B., Chan, A. E., & Ozburn, A. R. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109074 · Cited by 13
Investigational therapies for the pharmacological treatment of alcoholism
Hillemacher, T., Leggio, L., & Heberlein, A. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.954037 · Cited by 10
Pirino, B. E., Hawks, A., Carpenter, B. A., Candelas, P. G., Gargiulo, A. T., Curtis, G. R., Karkhanis, A. N., & Barson, J. R. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01850-1 · Cited by 10
The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats
Uhari-Väänänen, J. K., Raasmaja, A., Bäckström, P., Oinio, V., Carroll, F. I., Airavaara, M., Kiianmaa, K., & Piepponen, P. T. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4868-x · Cited by 10
The selective κ-opioid receptor antagonist JDTic attenuates the alcohol deprivation effect in rats
Uhari-Väänänen, J. K., Eteläinen, T. S., Bäckström, P., Oinio, V., Carroll, F. I., Raasmaja, A., Kiianmaa, K., & Piepponen, P. T. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.10.003 · Cited by 9
Hashimoto, N., Habu, H., Takao, S., Sakamoto, S., Okahisa, Y., Matsuo, K., Takaki, M., Kishi, Y., & Yamada, N. (2022) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2022.109365 · Cited by 8
Farahbakhsh, Z. Z., Holleran, K. M., Sens, J. P., Fordahl, S. C., Mauterer, M. I., López, A. J., Carlson, V. C. C., Kiraly, D. D., Grant, K. A., Jones, S. R., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56715-y · Cited by 7
Age as a factor in stress and alcohol interactions: A critical role for the kappa opioid system
Diaz, M. R., Przybysz, K. R., & Rouzer, S. K. (2017) · Alcohol · doi:10.1016/j.alcohol.2017.10.002 · Cited by 7
Kappa opioid receptor control of motivated behavior revisited
Farahbakhsh, Z. Z., & Siciliano, C. A. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02226-9 · Cited by 8
Lepreux, G., Henricks, A. M., Wei, G., Go, B. S., Erikson, C. M., Abella, R. M., Pham, A., & Walker, B. M. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173840 · Cited by 6
Self-citationNeurobiology of an endophenotype: modeling the progression of alcohol addiction in rodents
Mahoney, M. K., & Olmstead, M. C. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.03.006 · Cited by 8
Species differences in the effects of the κ-opioid receptor antagonist zyklophin
SIROHI, S. K., Aldrich, J. V., & Walker, B. M. (2016) · Alcohol · doi:10.1016/j.alcohol.2015.11.012 · Cited by 6
Self-citationEffectiveness of Nalmefene in Binge Eating Disorder
Marazziti, D., Piccinni, A., Baroni, S., & Dell’Osso, L. (2015) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000427 · Cited by 5
Nosova, O., Bazov, I., Karpyak, V. M., Hallberg, M., & Bakalkin, G. Y. (2021) · Molecules · doi:10.3390/molecules26113458 · Cited by 4
Herman, M. A., & Quadir, S. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00170-5 · Cited by 27
Cholinergic mu-opioid receptor deletion alters reward preference and aversion-resistance
Beane, C., Lewis, D. G., Bruns, N., Pikus, K. L., Durfee, M. H., Zegarelli, R. A., Perry, T. W., Sandoval, O., & Radke, A. K. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110019 · Cited by 4
Alcohol dependence and opioid receptor —Pharmacological profile of nalmefene—
Ohgi, Y. (2020) · Folia Pharmacologica Japonica · doi:10.1254/fpj.19139 · Cited by 4
Neurobiology of negative reinforcement as a driving force in alcohol addiction
Vendruscolo, L. F., & Koob, G. F. (2026) · Neuron · doi:10.1016/j.neuron.2026.04.038 · Cited by 4
Soyka, M. (2013) · Der Nervenarzt · doi:10.1007/s00115-013-3843-3 · Cited by 2
Lopez, M. F., Misztak, P., Becker, H. C., Cowan, C. W., & Anderson, E. M. (2025) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70142 · Cited by 1
Denny, L., Robichon, K., Templeton, N., Kiernan, M., Prisinzano, T. E., Kivell, B. M., & Flamme, A. C. L. (2025) · Clinical & Translational Immunology · doi:10.1002/cti2.70069 · Cited by 1
Butelman, E. R., Reed, B., Yuferov, V. P., & Kreek, M. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00025-3 · Cited by 1
Qu’apporte la neurobiologie aux addictions ?
Lenoir, M., & Noble, F. (2016) · La Presse Médicale · doi:10.1016/j.lpm.2016.02.021 · Cited by 2
Serecigni, J. G., & de Barcelona, S. P. (2015)
Functional imaging of neural systems associated with alcohol reward and amphetamine toxicity
Dudek, M. (2016) · Työväentutkimus Vuosikirja
Serecigni, J. G., & de Barcelona, S. P. (2015)
Motivating Change in Addiction via Modulation of the Dark Side
Koob, G. F. (2018) · Nebraska Symposium on Motivation/The Nebraska symposium on motivation · doi:10.1007/978-3-319-96920-6_1
Molecular Adaptations in Mesolimbic Circuitry and Pathological Ethanol Intake
Hopf, F. W., & Stuber, G. D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405941-2.00004-3
(2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816793-9.00001-3
Hawks, A., Spodnick, M. B., Jennings, M. C., Nelson, C. M., Peng, M., Vaughan, G. J., Carpenter, B. A., Chung, C. N., Karkhanis, A. N., & Barson, J. R. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06931-7
Mu opioid receptors in the habenula : dissecting reward and aversion in addiction
Boulos, L. (2017) · theses.fr (ABES) · doi:10.70675/4ec6ce3az48cbz4a77za34ezb8b76b41f629 · Cited by 1
Nalmefene for Managing Alcohol-Related Disorders: An Overview
Hashimoto, N., & Takaki, M. (2026) · Springer eBooks · doi:10.1007/978-3-031-35658-2_55-1
Metadata
- Authors
- Nealey, K. A., Smith, A. W., Davis, S. M., Smith, D. G., & Walker, B. M.
- Affiliations
- Washington State University (US)
- Lundbeck (United States) (US)
- Corresponding author
- Walker, Brendan M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 61
- Issue
- 1-2
- Pages
- 35-42
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3955175
- OpenAlex
- W2054879676
- Cited by
- 133
- References
- 66
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 2 · 2019: 5 · 2018: 13 · 2017: 11 · 2016: 15 · 2015: 11 · 2014: 9 · 2013: 15 · 2012: 14
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA020394)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- kappa opioid receptor, nalmefene, ethanol dependence, nucleus accumbens shell, dynorphin, nor-binaltorphimine, CTOP, naltrindole, ethanol self-administration, ethanol withdrawal, opioid antagonists
- MeSH terms
- Ethanol, Alcoholism, Animals, Male, Naltrexone, Nucleus Accumbens, Self Administration, Rats, Wistar, Receptors, Opioid, kappa, Rats, Infusions, Intraventricular
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
