The Kappa Opioid Receptor: From Addiction to Depression, and Back

Laurence Lalanne1,2, Gülebru Ayrancı3,2, Brigitte L. Kieffer2, Pierre-Éric Lutz4
1CHU Strasbourg
2Institut de Génétique et de Biologie Moléculaire et Cellulaire
3Douglas Mental Health University Institute [Montréal]
4Institut des Neurosciences Cellulaires et Intégratives

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Volkow, 2011, Addiction: pulling at the neural threads of social behaviors, Neuron, 69, 599, 10.1016/j.neuron.2011.01.027

Bakken, 2007, Axis I and II disorders as long-term predictors of mental distress: a six-year prospective follow-up of substance-dependent patients, BMC Psychiatry, 7, 29, 10.1186/1471-244X-7-29

de Graaf, 2004, Pathways to comorbidity: the transition of pure mood, anxiety and substance use disorders into comorbid conditions in a longitudinal population-based study, J Affect Disord, 82, 461, 10.1016/j.jad.2004.03.001

Goldstein, 1979, Dynorphin-(1-13), an extraordinarily potent opioid peptide, Proc Natl Acad Sci U S A, 76, 6666, 10.1073/pnas.76.12.6666

Chavkin, 1982, Dynorphin is a specific endogenous ligand of the kappa opioid receptor, Science, 215, 413, 10.1126/science.6120570

Le Merrer, 2009, Reward processing by the opioid system in the brain, Physiol Rev, 89, 1379, 10.1152/physrev.00005.2009

Nestler, 2005, Is there a common molecular pathway for addiction?, Nat Neurosci, 8, 1445, 10.1038/nn1578

Pradhan, 2011, The delta opioid receptor: an evolving target for the treatment of brain disorders, Trends Pharmacol Sci, 32, 581, 10.1016/j.tips.2011.06.008

Lutz, 2013, The multiple facets of opioid receptor function: implications for addiction, Curr Opin Neurobiol, 23, 473, 10.1016/j.conb.2013.02.005

Lutz, 2013, Opioid receptors: distinct roles in mood disorders, Trends Neurosci, 36, 195, 10.1016/j.tins.2012.11.002

Charbogne, 2014, 15 years of genetic approaches in vivo for addiction research: opioid receptor and peptide gene knockout in mouse models of drug abuse, Neuropharmacology, 76, 204, 10.1016/j.neuropharm.2013.08.028

Chefer, 2013, Kappa opioid receptors on dopaminergic neurons are necessary for kappa-mediated place aversion, Neuropsychopharmacology, 38, 2623, 10.1038/npp.2013.171

Tejeda, 2013, Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission and conditioned place aversion, Neuropsychopharmacology, 38, 1770, 10.1038/npp.2013.76

Bruchas, 2011, Selective p38alpha MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction, Neuron, 71, 498, 10.1016/j.neuron.2011.06.011

Ahmad, 2013, Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus mu-opiate receptor dependent mechanisms, J Neurosci, 33, 15642, 10.1523/JNEUROSCI.1686-13.2013

Schindler, 2012, Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake, J Neurosci, 32, 17582, 10.1523/JNEUROSCI.3220-12.2012

Bruchas, 2010, The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors, Brain Res, 1314, 44, 10.1016/j.brainres.2009.08.062

Knoll, 2010, Dynorphin, stress, and depression, Brain Res, 1314, 56, 10.1016/j.brainres.2009.09.074

Berger, 2013, Affective cue-induced escalation of alcohol self-administration and increased 22-kHz ultrasonic vocalizations during alcohol withdrawal: role of kappa-opioid receptors, Neuropsychopharmacology, 38, 647, 10.1038/npp.2012.229

Smith, 2012, Stress-induced activation of the dynorphin/kappa-opioid receptor system in the amygdala potentiates nicotine conditioned place preference, J Neurosci, 32, 1488, 10.1523/JNEUROSCI.2980-11.2012

Kallupi, 2013, Kappa opioid receptor-mediated dysregulation of gamma-aminobutyric acidergic transmission in the central amygdala in cocaine addiction, Biol Psychiatry, 74, 520, 10.1016/j.biopsych.2013.04.028

Harrison, 2013, Trial watch: opioid receptor blocker shows promise in phase II depression trial, Nat Rev Drug Discov, 12, 415, 10.1038/nrd4028

Gerra, 2004, Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome, Drug Alcohol Depend, 75, 37, 10.1016/j.drugalcdep.2003.11.017

Gerra, 2006, Naltrexone and buprenorphine combination in the treatment of opioid dependence, J Psychopharmacol, 20, 806, 10.1177/0269881106060835

Pfeiffer, 1986, Psychotomimesis mediated by kappa opiate receptors, Science, 233, 774, 10.1126/science.3016896

Roth, 2002, Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist, Proc Natl Acad Sci U S A, 99, 11934, 10.1073/pnas.182234399

Shippenberg, 1986, Differential effects of mu and kappa opioid systems on motivational processes, NIDA Res Monogr, 75, 563

Nestler, 2006, The mesolimbic dopamine reward circuit in depression, Biol Psychiatry, 59, 1151, 10.1016/j.biopsych.2005.09.018

Di Chiara, 1988, Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats, Proc Natl Acad Sci U S A, 85, 5274, 10.1073/pnas.85.14.5274

Johnson, 1992, Opioids excite dopamine neurons by hyperpolarization of local interneurons, J Neurosci, 12, 483, 10.1523/JNEUROSCI.12-02-00483.1992

Jalabert, 2011, Neuronal circuits underlying acute morphine action on dopamine neurons, Proc Natl Acad Sci U S A, 108, 16446, 10.1073/pnas.1105418108

Matsui, 2014, Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal, Neuron, 82, 1346, 10.1016/j.neuron.2014.04.030

Spanagel, 1992, Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway, Proc Natl Acad Sci U S A, 89, 2046, 10.1073/pnas.89.6.2046

Metzger, 2001, Site- and time-specific gene targeting in the mouse, Methods, 24, 71, 10.1006/meth.2001.1159

Backman, 2006, Characterization of a mouse strain expressing Cre recombinase from the 3’ untranslated region of the dopamine transporter locus, Genesis, 44, 383, 10.1002/dvg.20228

Paterson, 2007, Animal models and treatments for addiction and depression co-morbidity, Neurotox Res, 11, 1, 10.1007/BF03033479

Land, 2008, The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system, J Neurosci, 28, 407, 10.1523/JNEUROSCI.4458-07.2008

Land, 2009, Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking, Proc Natl Acad Sci U S A, 106, 19168, 10.1073/pnas.0910705106

Al-Hasani, 2013, Locus coeruleus kappa-opioid receptors modulate reinstatement of cocaine place preference through a noradrenergic mechanism, Neuropsychopharmacology, 38, 2484, 10.1038/npp.2013.151

Lemos, 2012, Repeated stress dysregulates kappa-opioid receptor signaling in the dorsal raphe through a p38alpha MAPK-dependent mechanism, J Neurosci, 32, 12325, 10.1523/JNEUROSCI.2053-12.2012

Beardsley, 2005, Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats, Psychopharmacology, 183, 118, 10.1007/s00213-005-0167-4

Mague, 2003, Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats, J Pharmacol Exp Ther, 305, 323, 10.1124/jpet.102.046433

Shirayama, 2004, Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects, J Neurochem, 90, 1258, 10.1111/j.1471-4159.2004.02589.x

Carlezon, 2006, Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats, J Pharmacol Exp Ther, 316, 440, 10.1124/jpet.105.092304

Falcon, 2014, Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice, Psychopharmacology, 10.1007/s00213-014-3723-y

Cohen, 2014, Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization, PLoS One, 9, e97216, 10.1371/journal.pone.0097216

Muschamp, 2014, Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area, Proc Natl Acad Sci U S A, 111, E1648, 10.1073/pnas.1315542111

Li, 2014, Opposing roles of cotransmission of dynorphin and hypocretin on reward and motivation, Proc Natl Acad Sci U S A, 111, 5765, 10.1073/pnas.1403603111

Bals-Kubik, 1993, Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats, J Pharmacol Exp Ther, 264, 489

Svingos, 2001, Major coexpression of kappa-opioid receptors and the dopamine transporter in nucleus accumbens axonal profiles, Synapse, 42, 185, 10.1002/syn.10005

Meshul, 2000, Kappa opioid receptor immunoreactivity in the nucleus accumbens and caudate-putamen is primarily associated with synaptic vesicles in axons, Neuroscience, 96, 91, 10.1016/S0306-4522(99)90481-5

Hjelmstad, 2003, Kappa opioid receptor activation in the nucleus accumbens inhibits glutamate and GABA release through different mechanisms, J Neurophysiol, 89, 2389, 10.1152/jn.01115.2002

Svingos, 2002, Kappa-opioid and NMDA glutamate receptors are differentially targeted within rat medial prefrontal cortex, Brain Res, 946, 262, 10.1016/S0006-8993(02)02894-9

Margolis, 2003, Kappa-opioid agonists directly inhibit midbrain dopaminergic neurons, J Neurosci, 23, 9981, 10.1523/JNEUROSCI.23-31-09981.2003

Margolis, 2006, Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex, Proc Natl Acad Sci U S A, 103, 2938, 10.1073/pnas.0511159103

Ekstrand, 2014, Molecular profiling of neurons based on connectivity, Cell, 157, 1230, 10.1016/j.cell.2014.03.059

Erbs, 2014, A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks, Brain Struct Funct, 10.1007/s00429-014-0717-9

Scherrer, 2006, Knockin mice expressing fluorescent delta-opioid receptors uncover G protein-coupled receptor dynamics in vivo, Proc Natl Acad Sci U S A, 103, 9691, 10.1073/pnas.0603359103

Wee, 2010, The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse, Psychopharmacology, 210, 121, 10.1007/s00213-010-1825-8

Kuzmin, 1997, Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice, Eur J Pharmacol, 321, 265, 10.1016/S0014-2999(96)00961-2

Glick, 1995, Kappa opioid inhibition of morphine and cocaine self-administration in rats, Brain Res, 681, 147, 10.1016/0006-8993(95)00306-B

Nestby, 1999, Bremazocine reduces unrestricted free-choice ethanol self-administration in rats without affecting sucrose preference, Psychopharmacology, 142, 309, 10.1007/s002130050894

Lindholm, 2001, The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat, Behav Brain Res, 120, 137, 10.1016/S0166-4328(00)00368-5

Logrip, 2009, Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H, Alcohol, 43, 359, 10.1016/j.alcohol.2009.05.001

Negus, 1997, Effects of kappa opioids on cocaine self-administration by rhesus monkeys, J Pharmacol Exp Ther, 282, 44

Mello, 1998, Effects of kappa opioid agonists on cocaine- and food-maintained responding by rhesus monkeys, J Pharmacol Exp Ther, 286, 812

Schenk, 2001, Effects of the kappa-opioid receptor agonist, U69593, on the development of sensitization and on the maintenance of cocaine self-administration, Neuropsychopharmacology, 24, 441, 10.1016/S0893-133X(00)00190-1

Schenk, 1999, U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking, Psychopharmacology, 144, 339, 10.1007/s002130051016

Galeote, 2009, Prodynorphin gene disruption increases the sensitivity to nicotine self-administration in mice, Int J Neuropsychopharmacol, 12, 615, 10.1017/S1461145708009450

Mendizabal, 2006, Involvement of kappa/dynorphin system in WIN 55,212-2 self-administration in mice, Neuropsychopharmacology, 31, 1957, 10.1038/sj.npp.1300957

Maisonneuve, 1994, U50,488, a kappa opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens of rats, Neurosci Lett, 181, 57, 10.1016/0304-3940(94)90559-2

Femenia, 2011, Increased ethanol intake in prodynorphin knockout mice is associated to changes in opioid receptor function and dopamine transmission, Addict Biol, 17, 322, 10.1111/j.1369-1600.2011.00378.x

Resendez, 2012, Kappa-opioid receptors within the nucleus accumbens shell mediate pair bond maintenance, J Neurosci, 32, 6771, 10.1523/JNEUROSCI.5779-11.2012

Vanderschuren, 1995, Mu- and kappa-opioid receptor-mediated opioid effects on social play in juvenile rats, Eur J Pharmacol, 276, 257, 10.1016/0014-2999(95)00040-R

Trezza, 2010, The pleasures of play: pharmacological insights into social reward mechanisms, Trends Pharmacol Sci, 31, 463, 10.1016/j.tips.2010.06.008

Robles, 2014, Effects of kappa opioid receptors on conditioned place aversion and social interaction in males and females, Behav Brain Res, 262, 84, 10.1016/j.bbr.2014.01.003

Carlezon, 2007, Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation, Nat Protoc, 2, 2987, 10.1038/nprot.2007.441

Todtenkopf, 2004, Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats, Psychopharmacology, 172, 463, 10.1007/s00213-003-1680-y

Potter, 2011, Repeated exposure to the kappa-opioid receptor agonist salvinorin A modulates extracellular signal-regulated kinase and reward sensitivity, Biol Psychiatry, 70, 744, 10.1016/j.biopsych.2011.05.021

Solomon, 1973, An opponent-process theory of motivation. II Cigarette addiction, J Abnorm Psychol, 81, 158, 10.1037/h0034534

Koob, 2008, Review. Neurobiological mechanisms for opponent motivational processes in addiction, Philos Trans R Soc Lond B Biol Sci, 363, 3113, 10.1098/rstb.2008.0094

Thompson, 2000, Kappa-opioid receptor activation modifies dopamine uptake in the nucleus accumbens and opposes the effects of cocaine, J Neurosci, 20, 9333, 10.1523/JNEUROSCI.20-24-09333.2000

Ebner, 2010, Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens, Psychopharmacology, 210, 241, 10.1007/s00213-010-1836-5

Gehrke, 2008, Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum, Psychopharmacology, 197, 509, 10.1007/s00213-007-1067-6

Zhang, 2005, Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors, Psychopharmacology, 179, 551, 10.1177/0269881105056526

Muschamp, 2011, Activation of CREB in the nucleus accumbens shell produces anhedonia and resistance to extinction of fear in rats, J Neurosci, 31, 3095, 10.1523/JNEUROSCI.5973-10.2011

Russell, 2014, Sex differences in sensitivity to the depressive-like effects of the kappa opioid receptor agonist u-50488 in rats, Biol Psychiatry, 76, 213, 10.1016/j.biopsych.2013.07.042

Newton, 2002, Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect, J Neurosci, 22, 10883, 10.1523/JNEUROSCI.22-24-10883.2002

del Rosario Capriles, 2002, Motivational effects mu- and kappa-opioid agonists following acute and chronic restraint stress: involvement of dopamine D(1) and D(2) receptors, Behav Brain Res, 132, 159, 10.1016/S0166-4328(01)00414-4

McLaughlin, 2003, Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses, J Neurosci, 23, 5674, 10.1523/JNEUROSCI.23-13-05674.2003

Miczek, 2008, Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake, Pharmacol Ther, 120, 102, 10.1016/j.pharmthera.2008.07.006

McLaughlin, 2006, Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system, Neuropsychopharmacology, 31, 1241, 10.1038/sj.npp.1300872

Krishnan, 2007, Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions, Cell, 131, 391, 10.1016/j.cell.2007.09.018

Berube, 2013, Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat stress, Physiol Behav, 122, 237, 10.1016/j.physbeh.2013.04.009

Nocjar, 2012, The social defeat animal model of depression shows diminished levels of orexin in mesocortical regions of the dopamine system, and of dynorphin and orexin in the hypothalamus, Neuroscience, 218, 138, 10.1016/j.neuroscience.2012.05.033

Chaudhury, 2013, Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons, Nature, 493, 532, 10.1038/nature11713

Tao, 2002, Opioid receptor subtypes differentially modulate serotonin efflux in the rat central nervous system, J Pharmacol Exp Ther, 303, 549, 10.1124/jpet.102.037861

Tao, 2005, mu-opioids disinhibit and kappa-opioids inhibit serotonin efflux in the dorsal raphe nucleus, Brain Res, 1049, 70, 10.1016/j.brainres.2005.04.076

Zhang, 2007, Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies, Eur J Pharmacol, 570, 89, 10.1016/j.ejphar.2007.05.045

Belmaker, 2008, Major depressive disorder, N Engl J Med, 358, 55, 10.1056/NEJMra073096

Koob, 2010, Neurocircuitry of addiction, Neuropsychopharmacology, 35, 217, 10.1038/npp.2009.110

Sinha, 2006, Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes, Arch Gen Psychiatry, 63, 324, 10.1001/archpsyc.63.3.324

Aldrich, 2009, Zyklophin, a systemically active selective kappa opioid receptor peptide antagonist with short duration of action, Proc Natl Acad Sci U S A, 106, 18396, 10.1073/pnas.0910180106

Redila, 2008, Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system, Psychopharmacology, 200, 59, 10.1007/s00213-008-1122-y

McLaughlin, 2006, Prior activation of kappa opioid receptors by U50,488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning, Neuropsychopharmacology, 31, 787, 10.1038/sj.npp.1300860

Sperling, 2010, Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration, Psychopharmacology, 210, 199, 10.1007/s00213-010-1844-5

Kreibich, 2008, Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system, J Neurosci, 28, 6516, 10.1523/JNEUROSCI.0390-08.2008

Reyes, 2009, Subcellular targeting of kappa-opioid receptors in the rat nucleus locus coeruleus, J Comp Neurol, 512, 419, 10.1002/cne.21880

Zhou, 2013, Involvement of dynorphin and kappa opioid receptor in yohimbine-induced reinstatement of heroin seeking in rats, Synapse, 67, 358, 10.1002/syn.21638

Lutz, 2013, Multiple serotonergic paths to antidepressant efficacy, J Neurophysiol, 109, 2245, 10.1152/jn.01093.2012

McDevitt, 2011, Regulation of dorsal raphe nucleus function by serotonin autoreceptors: a behavioral perspective, J Chem Neuroanat, 41, 234, 10.1016/j.jchemneu.2011.05.001

Graziane, 2013, Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity, Neuron, 77, 942, 10.1016/j.neuron.2012.12.034

Polter, 2014, Poststress block of kappa opioid receptors rescues long-term potentiation of inhibitory synapses and prevents reinstatement of cocaine seeking, Biol Psychiatry, 10.1016/j.biopsych.2014.04.019

Sivam, 1989, Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism, J Pharmacol Exp Ther, 250, 818

Solecki, 2009, Alterations of prodynorphin gene expression in the rat mesocorticolimbic system during heroin self-administration, Brain Res, 1255, 113, 10.1016/j.brainres.2008.12.002

Przewlocka, 1997, Ethanol withdrawal enhances the prodynorphin system activity in the rat nucleus accumbens, Neurosci Lett, 238, 13, 10.1016/S0304-3940(97)00829-X

Lindholm, 2000, Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain, Alcohol, 22, 165, 10.1016/S0741-8329(00)00118-X

D’Addario, 2013, Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain, Addict Biol, 18, 425, 10.1111/j.1369-1600.2011.00326.x

Muschamp, 2013, Roles of nucleus accumbens CREB and dynorphin in dysregulation of motivation, Cold Spring Harb Perspect Med, 3, a012005, 10.1101/cshperspect.a012005

Bazov, 2013, The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction, Addict Biol, 18, 161, 10.1111/j.1369-1600.2011.00366.x

Rassnick, 1993, Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal, Brain Res, 605, 25, 10.1016/0006-8993(93)91352-S

Rasmussen, 2001, Chronic daily ethanol and withdrawal: 2. Behavioral changes during prolonged abstinence, Alcohol Clin Exp Res, 25, 999, 10.1111/j.1530-0277.2001.tb02308.x

Valdez, 2004, Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation, Alcohol Clin Exp Res, 28, 865, 10.1097/01.ALC.0000128222.29875.40

Valdez, 2003, Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence, Alcohol, 29, 55, 10.1016/S0741-8329(03)00020-X

Valdez, 2012, kappa opioid regulation of anxiety-like behavior during acute ethanol withdrawal, Pharmacol Biochem Behav, 102, 44, 10.1016/j.pbb.2012.03.019

Williams, 2012, The effect of intermittent alcohol vapor or pulsatile heroin on somatic and negative affective indices during spontaneous withdrawal in Wistar rats, Psychopharmacology, 223, 75, 10.1007/s00213-012-2691-3

Kessler, 2012, Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the national comorbidity survey replication adolescent supplement, Arch Gen Psychiatry, 69, 372, 10.1001/archgenpsychiatry.2011.160

Barnett, 2012, Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study, Lancet, 380, 37, 10.1016/S0140-6736(12)60240-2

Cerda, 2008, Comorbid forms of psychopathology: key patterns and future research directions, Epidemiol Rev, 30, 155, 10.1093/epirev/mxn003

Kissler, 2014, The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors, Biol Psychiatry, 75, 774, 10.1016/j.biopsych.2013.03.014

Wright, 2011, Toward affective circuit-based preclinical models of depression: sensitizing dorsal PAG arousal leads to sustained suppression of positive affect in rats, Neurosci Biobehav Rev, 35, 1902, 10.1016/j.neubiorev.2011.08.004

Milligan, 2003, Principles: extending the utility of [35S]GTP gamma S binding assays, Trends Pharmacol Sci, 24, 87, 10.1016/S0165-6147(02)00027-5

Kang-Park, 2013, kappa-opioid receptors in the central amygdala regulate ethanol actions at presynaptic GABAergic Sites, J Pharmacol Exp Ther, 346, 130, 10.1124/jpet.112.202903

Kenny, 2006, Conditioned withdrawal drives heroin consumption and decreases reward sensitivity, J Neurosci, 26, 5894, 10.1523/JNEUROSCI.0740-06.2006

Gillett, 2013, Protracted withdrawal from ethanol and enhanced responsiveness stress: Regulation via the dynorphin/kappa opioid receptor system, Alcohol, 47, 359, 10.1016/j.alcohol.2013.05.001

Goeldner, 2011, Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine, Biol Psychiatry, 69, 236, 10.1016/j.biopsych.2010.08.021

Lutz, 2013, A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice, Behav Brain Res, 243, 44, 10.1016/j.bbr.2012.12.049

Lutz, 2011, Sequential and opposing alterations of 5-HT(1A) receptor function during withdrawal from chronic morphine, Eur Neuropsychopharmacol, 21, 835, 10.1016/j.euroneuro.2011.02.002

Lutz, 2014, Distinct mu, delta and kappa opioid receptor mechanisms underlie low sociability and depressive-like behaviors during heroin abstinence, Neuropsychopharmacology, 39, 2694, 10.1038/npp.2014.126

Belin, 2008, High impulsivity predicts the switch to compulsive cocaine-taking, Science, 320, 1352, 10.1126/science.1158136

Deroche-Gamonet, 2004, Evidence for addiction-like behavior in the rat, Science, 305, 1014, 10.1126/science.1099020

Spetea, 2013, Current kappa opioid receptor ligands and discovery of a new molecular scaffold as a kappa opioid receptor antagonist using pharmacophore-based virtual screening, Curr Pharm Des, 19, 7362, 10.2174/138161281942140105162601

Dean, 2004, Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence, Eur Psychiatry, 19, 510, 10.1016/j.eurpsy.2004.09.002

Rorick-Kehn, 2014, LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders, Neuropharmacology, 77, 131, 10.1016/j.neuropharm.2013.09.021

Urbano, 2014, Antagonists of the kappa opioid receptor, Bioorg Med Chem Lett, 24, 2021, 10.1016/j.bmcl.2014.03.040

Carroll, 2013, Development of kappa opioid receptor antagonists, J Med Chem, 56, 2178, 10.1021/jm301783x

Melief, 2011, Duration of action of a broad range of selective kappa-opioid receptor antagonists is positively correlated with c-Jun N-terminal kinase-1 activation, Mol Pharmacol, 80, 920, 10.1124/mol.111.074195

Melief, 2010, Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling, Proc Natl Acad Sci U S A, 107, 11608, 10.1073/pnas.1000751107

Pradhan, 2012, Ligand-directed signalling within the opioid receptor family, Br J Pharmacol, 167, 960, 10.1111/j.1476-5381.2012.02075.x

Al-Hasani, 2011, Molecular mechanisms of opioid receptor-dependent signaling and behavior, Anesthesiology, 115, 1363, 10.1097/ALN.0b013e318238bba6

Schattauer, 2012, Ligand directed signaling differences between rodent and human kappa-opioid receptors, J Biol Chem, 287, 41595, 10.1074/jbc.M112.381368

Wang, 2014, The association of genetic polymorphisms in the kappa-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance, J Clin Psychopharmacol, 34, 205, 10.1097/JCP.0000000000000082

Nielsen, 2013, The kappa-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial, Psychiatr Genet, 23, 225, 10.1097/YPG.0000000000000008

Gerra, 2014, Association between gene variants and response to buprenorphine maintenance treatment, Psychiatry Res, 215, 202, 10.1016/j.psychres.2013.11.001

Zheng, 2013, Synthesis and evaluation of 11C-LY2795050 as a kappa-opioid receptor antagonist radiotracer for PET imaging, J Nucl Med, 54, 455, 10.2967/jnumed.112.109512

Markou, 1998, Neurobiological similarities in depression and drug dependence: a self-medication hypothesis, Neuropsychopharmacology, 18, 135, 10.1016/S0893-133X(97)00113-9

Hill, 2012, Neurobiology of chronic mild stress: parallels to major depression, Neurosci Biobehav Rev, 36, 2085, 10.1016/j.neubiorev.2012.07.001

Willner, 2005, Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS, Neuropsychobiology, 52, 90, 10.1159/000087097

Bambico, 2013, Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis?, Curr Top Behav Neurosci, 15, 243, 10.1007/7854_2012_234

Papp, 1991, An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress, Psychopharmacology, 104, 255, 10.1007/BF02244188

Valverde, 1997, The attenuation of morphine-conditioned place preference following chronic mild stress is reversed by a CCKB receptor antagonist, Psychopharmacology, 131, 79, 10.1007/s002130050268

Al-Hasani, 2013, Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference, Front Pharmacol, 4, 96, 10.3389/fphar.2013.00096

Lanteri, 2014, Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons, Mol Psychiatry, 19, 823, 10.1038/mp.2013.97

Tassin, 2008, Uncoupling between noradrenergic and serotonergic neurons as a molecular basis of stable changes in behavior induced by repeated drugs of abuse, Biochem Pharmacol, 75, 85, 10.1016/j.bcp.2007.06.038

Pietrzak, 2014, Association of in vivo kappa-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology, JAMA Psychiatry, 71, 1262, 10.1001/jamapsychiatry.2014.1221