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.
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
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 effects of k-opioid receptor blockade on high compulsive-like alcohol intake may be mediated by the extended amygdala, including the CeA and shell of the NAc.
“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
The Discussion reports that blocking κ-opioid receptors in the nucleus accumbens shell attenuated excessive ethanol self-administration in dependent rats. It does not identify the central amygdala (CeA) or establish the extended amygdala as the mediating circuit; it also describes excessive intake rather than specifically compulsive-like intake. (LLM, conf=0.86)
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.
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
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 · see citing works
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733 · see citing works
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 4,420 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Di Chiara, G., & Imperato, A. (1988) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24578-5 · Cited by 916 · see citing works
Psychotomimesis Mediated by κ Opiate Receptors
Pfeiffer, A., Brantl, V., Herz, A., & Emrich, H. M. (1986) · Science · doi:10.1126/science.3016896 · Cited by 857 · see citing works
Neurobiological similarities in depression and drug dependence: a self-medication hypothesis
Markou, A. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00113-9 · Cited by 767 · see citing works
Corticostriatal-hypothalamic circuitry and food motivation: Integration of energy, action and reward
Kelley, A. E., Baldo, B. A., Pratt, W. E., & Will, M. J. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.08.066 · Cited by 752 · see citing works
Samson, H. H. (1986) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1986.tb05120.x · Cited by 670 · see citing works
Ventral Tegmental Area Neurons in Learned Appetitive Behavior and Positive Reinforcement
Fields, H. L., Hjelmstad, G. O., Margolis, E. B., & Nicola, S. M. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094341 · Cited by 611 · see citing works
The Dysphoric Component of Stress Is Encoded by Activation of the Dynorphin κ-Opioid System
Land, B. B., Bruchas, M. R., Lemos, J. C., Xu, M., Melief, E. J., & Chavkin, C. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4458-07.2008 · Cited by 601 · see citing works
Opioid modulation of taste hedonics within the ventral striatum
Kelley, A. E., Bakshi, V. P., Haber, S. N., Steininger, T. L., Will, M. J., & Zhang, M. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00751-5 · Cited by 526 · see citing works
Mucha, R. F., & Herz, A. (1985) · Psychopharmacology · doi:10.1007/bf00432213 · Cited by 515 · see citing works
A key role for corticotropin-releasing factor in alcohol dependence
Heilig, M., & Koob, G. F. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.006 · Cited by 503 · cited 1× · see citing works
“N IH -PA Author M anuscript N IH -PA Author M anuscript emotional states that accompany acute and protracted withdrawal from alcohol (Heilig and Koob 2007).”
BackgroundAntidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats
Mague, S. D., Pliakas, A. M., Todtenkopf, M. S., Tomasiewicz, H. C., Zhang, Y., Stevens, W. C., Jones, R. M., Portoghese, P. S., & Carlezon, W. A. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.046433 · Cited by 485 · see citing works
Pharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence
Walker, B. M., & Koob, G. F. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301438 · Cited by 392 · see citing works
Self-citationCarlezon, W. A., Béguin, C., DiNieri, J. A., Baumann, M. H., Richards, M. R., Todtenkopf, M. S., Rothman, R. B., Ma, Z., Lee, D. Y.-W., & Cohen, B. M. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.092304 · Cited by 390 · see citing works
Valdez, G. R., Roberts, A. J., Chan, K., Davis, H., Brennan, M., Zorrilla, E. P., & Koob, G. F. (2002) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02448.x · Cited by 387 · see citing works
Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms
Heilig, M. A., & Egli, M. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.02.001 · Cited by 378 · see citing works
Gonzales, R. A., & Weiss, F. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-24-10663.1998 · Cited by 351 · see citing works
Excessive Ethanol Drinking Following a History of Dependence Animal Model of Allostasis
Roberts, A. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00167-0 · Cited by 349 · see citing works
Enhanced Alcohol Self‐Administration after Intermittent Versus Continuous Alcohol Vapor Exposure
O’Dell, L. E., Roberts, A. J., Smith, R. T., & Koob, G. F. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000145781.11923.4e · Cited by 342 · see citing works
Hormone-neurotransmitter interactions in the control of sexual behavior
Hull, E. M., Lorrain, D. S., Du, J., Matuszewich, L., Lumley, L. A., Putnam, S. K., & Moses, J. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00086-8 · Cited by 329 · see citing works
Neurobiology of Addiction: Toward the Development of New Therapies
Koob, G. F. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06682.x · Cited by 314 · see citing works
Land, B. B., Bruchas, M. R., Schattauer, S., Giardino, W. J., Aita, M., Messinger, D., Hnasko, T. S., Palmiter, R. D., & Chavkin, C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910705106 · Cited by 301 · see citing works
Effects of κ-opioid receptor ligands on intracranial self-stimulation in rats
Todtenkopf, M. S., Marcus, J. F., Portoghese, P. S., & Carlezon, W. A. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1680-y · Cited by 273 · see citing works
Mason, B. J., Ritvo, E. C., Morgan, R. O., Salvato, F., Goldberg, G., Welch, B., & Mantero-atienza, E. (1994) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1994.tb00098.x · Cited by 248 · see citing works
Enhanced Sensitivity of Pituitary βEndorphin to Ethanol in Subjects at High Risk of Alcoholism
Gianoulakis, C. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830030072011 · Cited by 224 · see citing works
Walker, B. M., Zorrilla, E. P., & Koob, G. F. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00226.x · Cited by 202 · see citing works
Self-citationWalker, B. M., & Koob, G. F. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00259.x · Cited by 196 · see citing works
Self-citationValdez, G. R., Roberts, A., Chan, K., Davis, H., Brennan, M., Zorrilla, E. P., & Koob, G. F. (2002) · PubMed · doi:10.1097/01.alc.0000033120.51856.f0 · Cited by 187 · see citing works
Nucleus accumbens cell firing during goal-directed behaviors for cocaine vs. ‘natural’ reinforcement
Carelli, R. M. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00760-6 · Cited by 183 · see citing works
Polydipsia Elicited by the Synergistic Action of a Saccharin and Glucose Solution
Valenstein, E. S., Cox, V. C., & Kakolewski, J. W. (1967) · Science · doi:10.1126/science.157.3788.552 · Cited by 148 · see citing works
Bart, G. B., Schluger, J. H., Borg, L., Ho, A., Bidlack, J. M., & Kreek, M. J. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300811 · Cited by 143 · see citing works
Hyytiä, P., & Kiianmaa, K. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02123.x · Cited by 140 · see citing works
Broadbear, J. H., Negus, S. S., Butelman, E. R., de Costa, B. R., & Woods, J. H. (1994) · Psychopharmacology · doi:10.1007/bf02245071 · Cited by 139 · see citing works
Stromberg, M. F., Casale, M., Volpicelli‐Daley, L. A., Volpicelli, J. R., & O’Brien, C. P. (1998) · Alcohol · doi:10.1016/s0741-8329(97)00131-6 · Cited by 139 · see citing works
Lindholm, S., Ploj, K., Franck, J., & Nylander, I. (2000) · Alcohol · doi:10.1016/s0741-8329(00)00118-x · Cited by 123 · see citing works
Marinelli, P. W., Quirion, R., & Gianoulakis, C. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1490-2 · Cited by 122 · see citing works
Binding of a new opiate antagonist, nalmefene, to rat brain membranes.
Me, M., Bolger, G. T., & Weissman, B. A. (1985) · PubMed · Cited by 106 · see citing works
Marinelli, P. W., Quirion, R., & Gianoulakis, C. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.047 · Cited by 103 · see citing works
Marinelli, P. W., Lam, M. P., Bai, L., Quirion, R., & Gianoulakis, C. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00112.x · Cited by 98 · see citing works
Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake
Logrip, M. L., Janak, P. H., & Dorit Ron, A. (2008) · The FASEB Journal · doi:10.1096/fj.07-099135 · Cited by 96 · see citing works
Marinelli, P. W., Bai, L., Quirion, R., & Gianoulakis, C. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000183008.62955.2e · Cited by 93 · see citing works
Mitchell, J., Liang, M. T., & Fields, H. L. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0067-7 · Cited by 89 · see citing works
Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption
Stromberg, M. F., Mackler, S. A., Volpicelli, J. R., & O’Brien, C. P. (2001) · Alcohol · doi:10.1016/s0741-8329(00)00137-3 · Cited by 81 · see citing works
Ethanol withdrawal enhances the prodynorphin system activity in the rat nucleus accumbens
Przewłocka, B., Turchan, J., Lasoń, W., & Przewłocki, R. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00829-x · Cited by 80 · see citing works
Walker, B. M., Drimmer, D. A., Walker, J. L., Liu, T., Mathé, A. A., & Ehlers, C. L. (2010) · Alcohol · doi:10.1016/j.alcohol.2010.06.006 · Cited by 63 · see citing works
Self-citationAlvarez‐Jaimes, L., Stouffer, D. G., & Parsons, L. H. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06301.x · Cited by 61 · see citing works
June, H. L., Grey, C., Warren‐Reese, C., Durr, L. F., Ricks‐Cord, A., Johnson, A., McCane, S., Williams, L., Mason, D., Cummings, R., et al. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb05931.x · Cited by 55 · see citing works
Doyon, W. M., Howard, E. C., Shippenberg, T. S., & Gonzales, R. A. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.04.005 · Cited by 53 · see citing works
Dai, X., Thavundayil, J., & Gianoulakis, C. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000187599.17786.4a · Cited by 52 · see citing works
Maldonado, R. J. (2003) · Springer eBooks · doi:10.1007/978-3-7091-0541-2_1 · Cited by 51 · see citing works
June, H. L., Cummings, R., Eiler, W. J. A., Foster, K. L., McKay, P. F., Seyoum, R., García, M., McCane, S., Grey, C., Hawkins, S. E., et al. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300338 · Cited by 48 · see citing works
Low doses of naltrexone reduce palatability and consumption of ethanol in outbred rats
Coonfield, D. L., Hill, K., Kaczmarek, H. J., Ferraro, F. M., & Kiefer, S. W. (2002) · Alcohol · doi:10.1016/s0741-8329(01)00180-x · Cited by 46 · see citing works
Williams, K. L., & Woods, J. H. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03960.x · Cited by 46 · see citing works
Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens
Lindholm, S., Rosin, Å., Dahlin, I., Georgieva, J., & Franck, J. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.05.039 · Cited by 40 · see citing works
Shoemaker, W. J., Vavrousek-Jakuba, E., Arons, C., & Kwok, F.-C. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00290-5 · Cited by 26 · see citing works
Walker, B. M., & Ehlers, C. L. (2009) · Behavioral Neuroscience · doi:10.1037/a0016002 · Cited by 25 · see citing works
Self-citationMj, P., Mathewson, C., & Rm, A. (1996) · PubMed · Cited by 21 · see citing works
Dopamine Mechanisms and Cocaine Reward
Ikegami, A., & Duvauchelle, C. L. (2004) · International review of neurobiology · doi:10.1016/s0074-7742(04)62002-2 · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Walker BM Zorrilla EP Koob GF Systemic kappa-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats Addict Biol 2011 16 116 119 20579007 PMC2988980
Cited by
Sorted by citations
The Development and Maintenance of Drug Addiction
Wise, R. A., & Koob, G. F. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.261 · Cited by 561 · see citing works
Addiction as a stress surfeit disorder
Koob, G. F., Buck, C. L., Cohen, A., Edwards, S., Park, P. E., Schlosburg, J. E., Schmeichel, B., Vendruscolo, L. F., Wade, C. L., Whitfield, T. W., et al. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.024 · Cited by 483 · see citing works
Mann, K. F., Bladström, A., Torup, L., Gual, A., & van den Brink, W. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.020 · Cited by 485 · see citing works
The dark side of emotion: the addiction perspective
Koob, G. F. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.11.044 · Cited by 433 · see citing works
Addiction is a Reward Deficit and Stress Surfeit Disorder
Koob, G. F. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00072 · Cited by 397 · see citing works
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337 · see citing works
Negative reinforcement in drug addiction: the darkness within
Koob, G. F. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.03.011 · Cited by 338 · see citing works
Addiction and Stress: An Allostatic View
Koob, G. F., & Schulkin, J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.008 · Cited by 315 · see citing works
Uhl, G. R., Koob, G. F., & Cable, J. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13989 · Cited by 259 · see citing works
Neurocircuitry of alcohol addiction
Koob, G. F. (2014) · Handbook of clinical neurology · doi:10.1016/b978-0-444-62619-6.00003-3 · Cited by 227 · see citing works
Nalmefene: A Review of Its Use in the Treatment of Alcohol Dependence
Keating, G. M. (2013) · CNS Drugs · doi:10.1007/s40263-013-0101-y · Cited by 213 · see citing works
Influence of stress associated with chronic alcohol exposure on drinking
Becker, H. C. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.04.028 · Cited by 191 · see citing works
Alcohol Dependence, Withdrawal, and Relapse
Becker, H. C. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405941-2.00019-5 · Cited by 184 · see citing works
Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder
Burnette, E. M., Nieto, S. J., Grodin, E. N., Meredith, L. R., Hurley, B., Miotto, K., Gillis, A. J., & Ray, L. A. (2022) · Drugs · doi:10.1007/s40265-021-01670-3 · Cited by 169 · see citing works
Operant alcohol self-administration in dependent rats: Focus on the vapor model
Vendruscolo, L. F., & Roberts, A. J. (2014) · Alcohol · doi:10.1016/j.alcohol.2013.08.006 · Cited by 166 · see citing works
Escalation of drug self-administration as a hallmark of persistent addiction liability
Edwards, S., & Koob, G. F. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3283644d15 · Cited by 151 · see citing works
The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors
Kissler, J. L., Sirohi, S., Reis, D. J., Jansen, H. T., Quock, R. M., Smith, D. G., & Walker, B. M. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.03.014 · Cited by 145 · see citing works
Self-citationMechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
Rose, J. H., Karkhanis, A. N., Chen, R., Gioia, D., Lopez, M. F., Becker, H. C., McCool, B. A., & Jones, S. R. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv127 · Cited by 136 · see citing works
Existing and future drugs for the treatment of the dark side of addiction
Koob, G. F., & Mason, B. J. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103143 · Cited by 121 · see citing works
Schlosburg, J. E., Whitfield, T. W., Park, P. E., Crawford, E. F., George, O., Vendruscolo, L. F., & Koob, G. F. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1979-13.2013 · Cited by 119 · see citing works
Söderpalm, B., & Ericson, M. (2011) · Current topics in behavioral neurosciences · doi:10.1007/978-3-642-28720-6_170 · Cited by 117 · see citing works
Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependence
Walker, B. M., Valdez, G. R., McLaughlin, J. P., & Bakalkin, G. Y. (2012) · Alcohol · doi:10.1016/j.alcohol.2011.10.006 · Cited by 106 · see citing works
Self-citationSmith, J. S., Schindler, A. G., Martinelli, E., Gustin, R. M., Bruchas, M. R., & Chavkin, C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2980-11.2012 · Cited by 102 · see citing works
The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety
Schank, J. R., Goldstein, A., Rowe, K. E., King, C. E., Marusich, J. A., Wiley, J. L., Carroll, F. I., Thorsell, A., & Heilig, M. A. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00455.x · Cited by 101 · see citing works
Mann, K. F., Torup, L., Sørensen, P. S., Gual, A., Swift, R. M., Walker, B. M., & van den Brink, W. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.10.008 · Cited by 97 · see citing works
Self-citationNeuroclinical Framework for the Role of Stress in Addiction
Kwako, L. E., & Koob, G. F. (2017) · Chronic Stress · doi:10.1177/2470547017698140 · Cited by 99 · see citing works
Endogenous opiates and behavior: 2006
Bodnar, R. J. (2007) · Peptides · doi:10.1016/j.peptides.2007.09.002 · Cited by 91 · see citing works
Wallace, C. W., & Fordahl, S. C. (2021) · Nutrition Research Reviews · doi:10.1017/s0954422421000196 · Cited by 92 · see citing works
George, O., Koob, G. F., & Vendruscolo, L. F. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3623-1 · Cited by 84 · see citing works
Neurochemical mechanisms of alcohol withdrawal
Becker, H. C., & Mulholland, P. J. (2014) · Handbook of clinical neurology · doi:10.1016/b978-0-444-62619-6.00009-4 · Cited by 83 · see citing works
A systems medicine research approach for studying alcohol addiction
Spanagel, R., Durstewitz, D., Hansson, A. C., Heinz, A., Kiefer, F., Köhr, G., Matthäus, F., Nöthen, M. M., Noori, H. R., Obermayer, K., et al. (2013) · Addiction Biology · doi:10.1111/adb.12109 · Cited by 81 · see citing works
Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of Ethanol
Anderson, R. I., & Becker, H. C. (2017) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.13406 · Cited by 79 · see citing works
κ opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake
Whitfield, T. W., Schlosburg, J. E., Wee, S., Gould, A., George, O., Grant, Y., Zamora-Martinez, E. R., Edwards, S., Crawford, E., Vendruscolo, L. F., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1978-13.2015 · Cited by 75 · see citing works
Personalized Treatment of Alcohol Dependence
Kranzler, H. R., & McKay, J. R. (2012) · Current Psychiatry Reports · doi:10.1007/s11920-012-0296-5 · Cited by 72 · see citing works
Karkhanis, A. N., Huggins, K. N., Rose, J. H., & Jones, S. R. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.022 · Cited by 68 · see citing works
Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders
Niciu, M. J., & Arias, A. J. (2013) · CNS Drugs · doi:10.1007/s40263-013-0096-4 · Cited by 68 · see citing works
Koob, G. F. (2017) · Psychopharmacology · doi:10.1007/s00213-016-4484-6 · Cited by 66 · see citing works
Alcohol-induced plasticity in the dynorphin/kappa-opioid receptor system
SIROHI, S. K., Bakalkin, G. Y., & Walker, B. M. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00095 · Cited by 64 · see citing works
Self-citationBerger, A. L., Williams, A. M., McGinnis, M. M., & Walker, B. M. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.229 · Cited by 62 · see citing works
Self-citationKappa opioid regulation of anxiety-like behavior during acute ethanol withdrawal
Valdez, G. R., & Harshberger, E. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.03.019 · Cited by 61 · see citing works
Yardley, M. M., & Ray, L. A. (2016) · Addiction Biology · doi:10.1111/adb.12349 · Cited by 60 · see citing works
Endogenous opiates and behavior: 2011
Bodnar, R. J. (2012) · Peptides · doi:10.1016/j.peptides.2012.09.027 · Cited by 58 · see citing works
Dysregulation of brain stress systems mediates compulsive alcohol drinking
Tunstall, B. J., Carmack, S. A., Koob, G. F., & Vendruscolo, L. F. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.10.006 · Cited by 55 · see citing works
Williams, A. M., Reis, D. J., Powell, A. S., Neira, L. J., Nealey, K. A., Ziegler, C. E., Kloss, N. D., Bilimoria, J. L., Smith, C. E., & Walker, B. M. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2691-3 · Cited by 53 · see citing works
Self-citationSiciliano, C. A., Calipari, E. S., Yorgason, J. T., Lovinger, D. M., Mateo, Y., Jimenez, V. A., Helms, C. M., Grant, K. A., & Jones, S. R. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4239-4 · Cited by 53 · see citing works
Erikson, C. M., Wei, G., & Walker, B. M. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.07.034 · Cited by 50 · see citing works
Self-citationHansson, A. C., Gründer, G., Hirth, N., Noori, H. R., Spanagel, R., & Sommer, W. H. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.010 · Cited by 49 · see citing works
Emerging pharmacotherapies for alcohol use disorder
Mason, B. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.04.032 · Cited by 46 · see citing works
Gillett, K., Harshberger, E., & Valdez, G. R. (2013) · Alcohol · doi:10.1016/j.alcohol.2013.05.001 · Cited by 45 · see citing works
Smith, A. C. W., Nealey, K. A., Wright, J. W., & Walker, B. M. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.04.011 · Cited by 45 · see citing works
Self-citationMontesinos, J., Gil, A., & Guerri, C. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13416 · Cited by 45 · see citing works
Nalmefene: a new approach to the treatment of alcohol dependence
Paillé, F., & Martini, H. (2014) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s45666 · Cited by 44 · see citing works
Laramée, P., Brodtkorb, T., Rahhali, N., Knight, C., Barbosa, C., François, C., Toumi, M., Daeppen, J., & Rehm, J. T. (2014) · BMJ Open · doi:10.1136/bmjopen-2014-005376 · Cited by 44 · see citing works
Koob, G. F., & Vendruscolo, L. F. (2023) · Current topics in behavioral neurosciences · doi:10.1007/7854_2023_424 · Cited by 44 · see citing works
Kissler, J. L., & Walker, B. M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.183 · Cited by 43 · see citing works
Self-citationDeehan, G. A., McKinzie, D. L., Carroll, F. I., McBride, W. J., & Rodd, Z. A. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.03.006 · Cited by 42 · see citing works
Henricks, A. M., Berger, A. L., Lugo, J. M., Baxter-Potter, L. N., Bieniasz, K. V., Petrie, G. N., Sticht, M. A., Hill, M. N., & McLaughlin, R. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.05.023 · Cited by 40 · see citing works
Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking
Hamida, S. B., Boulos, L., McNicholas, M., Charbogne, P., & Kieffer, B. L. (2017) · Addiction Biology · doi:10.1111/adb.12576 · Cited by 38 · see citing works
Opioid modulators for alcohol dependence
Hillemacher, T., Heberlein, A., Muschler, M., Bleich, S., & Frieling, H. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.592139 · Cited by 41 · see citing works
Neuroscience of opiates for addiction medicine
Zhou, Y., & Leri, F. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.09.001 · Cited by 38 · see citing works
Long-term ethanol effects on acute stress responses: modulation by dynorphin
Rácz, I., Markert, A., Mauer, D., Stoffel‐Wagner, B., & Zimmer, A. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00494.x · Cited by 36 · see citing works
An Animal Model of Alcohol Dependence to Screen Medications for Treating Alcoholism
Becker, H. C., & Lopez, M. F. (2016) · International review of neurobiology · doi:10.1016/bs.irn.2016.02.006 · Cited by 32 · see citing works
Dynorphin and κ-Opioid Receptor Dysregulation in the Dopaminergic Reward System of Human Alcoholics
Bazov, I., Sarkisyan, D., Kononenko, O., Watanabe, H., Yakovleva, T., Hansson, A. C., Sommer, W. H., Spanagel, R., & Bakalkin, G. Y. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0844-4 · Cited by 34 · see citing works
Haun, H. L., Lebonville, C. L., Solomon, M. G., Griffin, W. C., Lopez, M. F., & Becker, H. C. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.01.002 · Cited by 33 · see citing works
Alcohol: A stimulant activating brain stress responsive systems with persistent neuroadaptation
Zhou, Y., & Kreek, M. J. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.05.044 · Cited by 33 · see citing works
Rose, J. L., Karkhanis, A. N., Steiniger‐Brach, B., & Jones, S. R. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081216 · Cited by 32 · see citing works
Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure
Siciliano, C. A., Karkhanis, A. N., Holleran, K. M., Melchior, J. R., & Jones, S. R. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_106 · Cited by 32 · see citing works
Dissociable Effects of Kappa-Opioid Receptor Activation on Impulsive Phenotypes in Wistar Rats
Walker, B. M., & Kissler, J. L. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.129 · Cited by 25 · see citing works
Self-citationTigecycline Reduces Ethanol Intake in Dependent and Nondependent Male and Female C57 BL /6J Mice
Bergeson, S. E., Nipper, M. A., Jensen, J. P., Helms, M. L., & Finn, D. A. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13251 · Cited by 25 · see citing works
Zhou, Y., Colombo, G., Niikura, K., Carai, M. A. M., Femenía, T., García‐Gutiérrez, M. S., Manzanares, J., Ho, A., Gessa, G. L., & Kreek, M. J. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01867.x · Cited by 24 · see citing works
Jarman, S., Haney, A. M., & Valdez, G. R. (2018) · PLoS ONE · doi:10.1371/journal.pone.0205016 · Cited by 23 · see citing works
Walker, B. M. (2012) · Alcohol · doi:10.1016/j.alcohol.2012.01.001 · Cited by 23 · see citing works
Self-citationGo, B. S., SIROHI, S. K., & Walker, B. M. (2019) · Addiction Biology · doi:10.1111/adb.12715 · Cited by 23 · see citing works
Self-citationHenricks, A. M., Berger, A. L., Lugo, J. M., Baxter-Potter, L. N., Bieniasz, K. V., Craft, R. M., & McLaughlin, R. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.08.032 · Cited by 21 · see citing works
Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488
Funk, D. R., Coen, K. M., Tamadon, S., & Lê, A. D. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.01.017 · Cited by 21 · see citing works
Fontaine, H. M., Silva, P. R., Neiswanger, C., Tran, R., Abraham, A. D., Land, B. B., Neumaier, J. F., & Chavkin, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01178-0 · Cited by 21 · see citing works
Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine
Cameron, C. M., Nieto, S. J., Bosler, L., Wong, M. H., Bishop, I., Mooney, L. J., & Cahill, C. M. (2021) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2021.10009 · Cited by 20 · see citing works
Calleja‐Conde, J., Echeverry‐Alzate, V., Giné, E., Bühler, K., Nadal, R. A., Maldonado, R. J., de Fonseca, F. R., Gual, A., & López‐Moreno, J. A. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13526 · Cited by 18 · see citing works
Zhou, Y., & Kreek, M. J. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.117.245621 · Cited by 19 · see citing works
Bazov, I., Sarkisyan, D., Kononenko, O., Watanabe, H., Karpyak, V. M., Yakovleva, T., & Bakalkin, G. Y. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0075-5 · Cited by 19 · see citing works
D’Addario, C., Shchetynsky, K., Pucci, M., Cifani, C., Gunnar, A., Vukojević, V. B., Padyukov, L., & Terenius, L. Y. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.03.012 · Cited by 18 · see citing works
Contribution of Dynorphin and Orexin Neuropeptide Systems to the Motivational Effects of Alcohol
Anderson, R. I., Moorman, D. E., & Becker, H. C. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_100 · Cited by 18 · see citing works
de Guglielmo, G., Simpson, S., Kimbrough, A., Conlisk, D., Baker, R., Cantor, M., Kallupi, M., & George, O. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109309 · Cited by 16 · see citing works
nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior
Harshberger, E., Gilson, E. A., Gillett, K., Stone, J. H., Amrani, L. E., & Valdez, G. R. (2016) · Journal of Addiction · doi:10.1155/2016/1084235 · Cited by 17 · see citing works
Drinking Levels and Profiles of Alcohol Addicted Rats Predict Response to Nalmefene
Foo, J. C., Vengeliene, V., Noori, H. R., Yamaguchi, I., Morita, K., Nakamura, T., Yamamoto, Y., & Spanagel, R. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00471 · Cited by 17 · see citing works
Alcohol and the dopamine system
Söderpalm, B., & Ericson, M. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.02.003 · Cited by 16 · see citing works
Wei, G., Sirohi, S., & Walker, B. M. (2022) · Addiction Biology · doi:10.1111/adb.13138 · Cited by 15 · see citing works
Self-citationLos Antagonistas de los Receptores Opioides en el Tratamiento del Alcoholismo
Serecigni, J. G. (2015) · Adicciones · doi:10.20882/adicciones.708 · Cited by 14 · see citing works
A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction
Koob, G. F., & Vendruscolo, L. F. (2025) · Alcohol · doi:10.1016/j.alcohol.2025.08.004 · Cited by 13 · see citing works
Nalmefene Hydrochloride: Potential Implications for Treating Alcohol and Opioid Use Disorder
Green, M., Veltri, C. A., & Grundmann, O. (2024) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s431270 · Cited by 13 · see citing works
The histone methyltransferase G9a mediates stress‐regulated alcohol drinking
Anderson, E. M., Lopez, M. F., Kastner, A., Mulholland, P. J., Becker, H. C., & Cowan, C. W. (2021) · Addiction Biology · doi:10.1111/adb.13060 · Cited by 13 · see citing works
Farahbakhsh, Z. Z., Song, K., Branthwaite, H. E., Erickson, K. R., Mukerjee, S., Nolan, S. O., & Siciliano, C. A. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01547-x · Cited by 13 · see citing works
Pirino, B. E., Kelley, A. M., Karkhanis, A. N., & Barson, J. R. (2023) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15078 · Cited by 13 · see citing works
Green, E. W., Byers, I. S., & Deutsch‐Link, S. (2023) · Clinical Therapeutics · doi:10.1016/j.clinthera.2023.09.017 · Cited by 13 · see citing works
Özkan-Kotiloğlu, S., Kaya-Akyüzlü, D., Yurdakul, R., Yıldırım, M. A., & İlhan, İ. Ö. (2023) · Alcohol and Alcoholism · doi:10.1093/alcalc/agad036 · Cited by 12 · see citing works
Accumbal μ‐Opioid Receptors Modulate Ethanol Intake in Alcohol‐Preferring Alko Alcohol Rats
Uhari-Väänänen, J. K., Raasmaja, A., Bäckström, P., Oinio, V., Airavaara, M., Piepponen, P. T., & Kiianmaa, K. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13176 · Cited by 12 · see citing works
Inhibition of Glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats
de Guglielmo, G., Conlisk, D., Barkley‐Levenson, A. M., Palmer, A. A., & George, O. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.03.001 · Cited by 11 · see citing works
Lepreux, G., Shinn, G. E., Wei, G., Suko, A. V., Concepcion, G., Sirohi, S., Go, B. S., Bruchas, M. R., & Walker, B. M. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109457 · Cited by 10 · see citing works
Self-citationTobin, S. J., Wakefield, D. L., Terenius, L. Y., Vukojević, V. B., & Jovanović‐Talisman, T. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00488 · Cited by 10 · see citing works
- 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
