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Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food

  • Pauline Charbogne
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch

    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Olivier Gardon
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch
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  • Elena Martín-García
    Affiliations
    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
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  • Helen L. Keyworth
    Affiliations
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom
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  • Aya Matsui
    Affiliations
    Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
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  • Anna E. Mechling
    Affiliations
    Department of Radiology, Medical Physics, Medical Center–University of Freiburg, Faculty of Medicine, Freiburg, Germany

    Faculty of Biology, University of Freiburg, Freiburg, Germany
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  • Thomas Bienert
    Affiliations
    Department of Radiology, Medical Physics, Medical Center–University of Freiburg, Faculty of Medicine, Freiburg, Germany
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  • Taufiq Nasseef
    Affiliations
    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Anne Robé
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch
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  • Luc Moquin
    Affiliations
    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Emmanuel Darcq
    Affiliations
    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Sami Ben Hamida
    Affiliations
    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Patricia Robledo
    Affiliations
    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
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  • Audrey Matifas
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch
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  • Katia Befort
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch

    Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg Faculté de Psychologie, Strasbourg, France

    Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, Centre National de la Recherche Scientifique, Strasbourg, France
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  • Claire Gavériaux-Ruff
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch
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  • Laura-Adela Harsan
    Affiliations
    Laboratory of Engineering, Informatics and Imaging, Integrative Multimodal Imaging in Healthcare, UMR 7357, University of Strasbourg, Strasbourg, France

    University Hospital Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg, France

    Department of Radiology, Medical Physics, Medical Center–University of Freiburg, Faculty of Medicine, Freiburg, Germany
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  • Dominik von Elverfeldt
    Affiliations
    Department of Radiology, Medical Physics, Medical Center–University of Freiburg, Faculty of Medicine, Freiburg, Germany
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  • Jurgen Hennig
    Affiliations
    Department of Radiology, Medical Physics, Medical Center–University of Freiburg, Faculty of Medicine, Freiburg, Germany
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  • Alain Gratton
    Affiliations
    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Ian Kitchen
    Affiliations
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom
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  • Alexis Bailey
    Affiliations
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom

    Institute of Medical and Biomedical Education, St. George’s University of London, London, United Kingdom
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  • Veronica A. Alvarez
    Affiliations
    Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
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  • Rafael Maldonado
    Affiliations
    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
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  • Brigitte L. Kieffer
    Correspondence
    Address correspondence to Brigitte L. Kieffer, Ph.D., McGill University, Department of Psychiatry, Douglas Mental Health Institute, 6875 Boulevard LaSalle, Montreal, QC H4H1R3, Canada;
    Affiliations
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch

    Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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Published:December 26, 2016DOI:https://doi.org/10.1016/j.biopsych.2016.12.022

      Abstract

      Background

      Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward.

      Methods

      We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food.

      Results

      Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures.

      Conclusions

      Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors.

      Keywords

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      References

        • Matthes H.W.
        • Maldonado R.
        • Simonin F.
        • Valverde O.
        • Slowe S.
        • Kitchen I.
        • et al.
        Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene.
        Nature. 1996; 383: 819-823
        • Charbogne P.
        • Kieffer B.L.
        • Befort K.
        15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse.
        Neuropharmacology. 2014; 76: 204-217
        • Moles A.
        • Kieffer B.L.
        • D’Amato F.R.
        Deficit in attachment behavior in mice lacking the mu-opioid receptor gene.
        Science. 2004; 304: 1983-1986
        • Le Merrer J.
        • Becker J.A.
        • Befort K.
        • Kieffer B.L.
        Reward processing by the opioid system in the brain.
        Physiol Rev. 2009; 89: 1379-1412
        • Russo S.J.
        • Nestler E.J.
        The brain reward circuitry in mood disorders.
        Nat Rev Neurosci. 2013; 14: 609-625
        • Lobo M.K.
        • Karsten S.L.
        • Gray M.
        • Geschwind D.H.
        • Yang X.W.
        FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains.
        Nat Neurosci. 2006; 9: 443-452
        • Erbs E.
        • Faget L.
        • Scherrer G.
        • Matifas A.
        • Filliol D.
        • Vonesch J.L.
        • et al.
        A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.
        Brain Struct Funct. 2015; 220: 677-702
        • Johnson S.W.
        • North R.A.
        Opioids excite dopamine neurons by hyperpolarization of local interneurons.
        J Neurosci. 1992; 12: 483-488
        • Kudo T.
        • Konno K.
        • Uchigashima M.
        • Yanagawa Y.
        • Sora I.
        • Minami M.
        • Watanabe M.
        GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis.
        Eur J Neurosci. 2014; 39: 1796-1809
        • Lowe J.D.
        • Bailey C.P.
        Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area.
        Br J Pharmacol. 2015; 172: 469-481
        • Miura M.
        • Saino-Saito S.
        • Masuda M.
        • Kobayashi K.
        • Aosaki T.
        Compartment-specific modulation of GABAergic synaptic transmission by mu-opioid receptor in the mouse striatum with green fluorescent protein-expressing dopamine islands.
        J Neurosci. 2007; 27: 9721-9728
        • Fields H.L.
        • Margolis E.B.
        Understanding opioid reward.
        Trends Neurosci. 2015; 38: 217-225
        • Wise R.A.
        • Rompre P.P.
        Brain dopamine and reward.
        Annu Rev Psychol. 1989; 40: 191-225
        • Matsui A.
        • Jarvie B.C.
        • Robinson B.G.
        • Hentges S.T.
        • Williams J.T.
        Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal.
        Neuron. 2014; 82: 1346-1356
        • Lammel S.
        • Lim B.K.
        • Ran C.
        • Huang K.W.
        • Betley M.J.
        • Tye K.M.
        • et al.
        Input-specific control of reward and aversion in the ventral tegmental area.
        Nature. 2012; 491: 212-217
        • Tan K.R.
        • Yvon C.
        • Turiault M.
        • Mirzabekov J.J.
        • Doehner J.
        • Labouebe G.
        • et al.
        GABA neurons of the VTA drive conditioned place aversion.
        Neuron. 2012; 73: 1173-1183
        • Pettit H.O.
        • Ettenberg A.
        • Bloom F.E.
        • Koob G.F.
        Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats.
        Psychopharmacology. 1984; 84: 167-173
        • Mechling A.E.
        • Hubner N.S.
        • Lee H.L.
        • Hennig J.
        • von Elverfeldt D.
        • Harsan L.A.
        Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI.
        Neuroimage. 2014; 96: 203-215
        • Mechling A.E.
        • Arefin T.
        • Lee H.L.
        • Bienert T.
        • Reisert M.
        • Ben Hamida S.
        • et al.
        Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.
        Proc Natl Acad Sci U S A. 2016; 113: 11603-11608
        • Weibel R.
        • Reiss D.
        • Karchewski L.
        • Gardon O.
        • Matifas A.
        • Filliol D.
        • et al.
        Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: Insight from conditional knockout mice.
        PLoS One. 2013; 8: e74706
        • Monory K.
        • Massa F.
        • Egertova M.
        • Eder M.
        • Blaudzun H.
        • Westenbroek R.
        • et al.
        The endocannabinoid system controls key epileptogenic circuits in the hippocampus.
        Neuron. 2006; 51: 455-466
        • Chu Sin Chung P.
        • Keyworth H.L.
        • Martin-Garcia E.
        • Charbogne P.
        • Darcq E.
        • Bailey A.
        • et al.
        A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons.
        Biol Psychiatry. 2015; 77: 404-415
        • Befort K.
        • Filliol D.
        • Darcq E.
        • Ghate A.
        • Matifas A.
        • Lardenois A.
        • et al.
        Gene expression is altered in the lateral hypothalamus upon activation of the mu opioid receptor.
        Ann N Y Acad Sci. 2008; 1129: 175-184
        • Slowe S.J.
        • Simonin F.
        • Kieffer B.
        • Kitchen I.
        Quantitative autoradiography of mu-, delta- and kappa1 opioid receptors in kappa-opioid receptor knockout mice.
        Brain Res. 1999; 818: 335-345
        • Berrendero F.
        • Castane A.
        • Ledent C.
        • Parmentier M.
        • Maldonado R.
        • Valverde O.
        Increase of morphine withdrawal in mice lacking A2a receptors and no changes in CB1/A2a double knockout mice.
        Eur J Neurosci. 2003; 17: 315-324
        • Contet C.
        • Filliol D.
        • Matifas A.
        • Kieffer B.L.
        Morphine-induced analgesic tolerance, locomotor sensitization and physical dependence do not require modification of mu opioid receptor, cdk5 and adenylate cyclase activity.
        Neuropharmacology. 2008; 54: 475-486
        • Tzschentke T.M.
        • Schmidt W.J.
        Morphine-induced catalepsy is augmented by NMDA receptor antagonists, but is partially attenuated by an AMPA receptor antagonist.
        Eur J Pharmacol. 1996; 295: 137-146
        • Le Merrer J.
        • Plaza-Zabala A.
        • Del Boca C.
        • Matifas A.
        • Maldonado R.
        • Kieffer B.L.
        Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.
        Biol Psychiatry. 2011; 69: 700-703
        • Martin-Garcia E.
        • Barbano M.F.
        • Galeote L.
        • Maldonado R.
        New operant model of nicotine-seeking behaviour in mice.
        Int J Neuropsychopharmacol. 2009; 12: 343-356
        • Burokas A.
        • Gutierrez-Cuesta J.
        • Martin-Garcia E.
        • Maldonado R.
        Operant model of frustrated expected reward in mice.
        Addict Biol. 2012; 17: 770-782
        • Barnett L.
        • Seth A.K.
        The MVGC multivariate Granger causality toolbox: A new approach to Granger-causal inference.
        J Neurosci Methods. 2014; 223: 50-68
        • Zhan Y.
        • Paolicelli R.C.
        • Sforazzini F.
        • Weinhard L.
        • Bolasco G.
        • Pagani F.
        • et al.
        Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior.
        Nat Neurosci. 2014; 17: 400-406
        • Contarino A.
        • Picetti R.
        • Matthes H.W.
        • Koob G.F.
        • Kieffer B.L.
        • Gold L.H.
        Lack of reward and locomotor stimulation induced by heroin in mu-opioid receptor-deficient mice.
        Eur J Pharmacol. 2002; 446: 103-109
        • Bailey A.
        • Metaxas A.
        • Al-Hasani R.
        • Keyworth H.L.
        • Forster D.M.
        • Kitchen I.
        Mouse strain differences in locomotor, sensitisation and rewarding effect of heroin; association with alterations in MOP-r activation and dopamine transporter binding.
        Eur J Neurosci. 2010; 31: 742-753
        • Serrano A.
        • Aguilar M.A.
        • Manzanedo C.
        • Rodriguez-Arias M.
        • Minarro J.
        Effects of DA D1 and D2 antagonists on the sensitisation to the motor effects of morphine in mice.
        Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26: 1263-1271
        • VanderWende C.
        • Spoerlein M.T.
        Morphine-induced catalepsy in mice: Modification by drugs acting on neurotransmitter systems.
        Neuropharmacology. 1979; 18: 633-637
        • Park Y.
        • Ho I.K.
        • Fan L.W.
        • Loh H.H.
        • Ko K.H.
        Region specific increase of dopamine receptor D1/D2 mRNA expression in the brain of mu-opioid receptor knockout mice.
        Brain Res. 2001; 894: 311-315
        • Di Chiara G.
        • Bassareo V.
        • Fenu S.
        • De Luca M.A.
        • Spina L.
        • Cadoni C.
        • et al.
        Dopamine and drug addiction: The nucleus accumbens shell connection.
        Neuropharmacology. 2004; 47: 227-241
        • Castro D.C.
        • Berridge K.C.
        Opioid hedonic hotspot in nucleus accumbens shell: mu, delta, and kappa maps for enhancement of sweetness “liking” and “wanting.”.
        J Neurosci. 2014; 34: 4239-4250
        • Koob G.F.
        • Volkow N.D.
        Neurocircuitry of addiction.
        Neuropsychopharmacology. 2010; 35: 217-238
        • Cui Y.
        • Ostlund S.B.
        • James A.S.
        • Park C.S.
        • Ge W.
        • Roberts K.W.
        • et al.
        Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.
        Nat Neurosci. 2014; 17: 254-261
        • Kupchik Y.M.
        • Scofield M.D.
        • Rice K.C.
        • Cheng K.
        • Roques B.P.
        • Kalivas P.W.
        Cocaine dysregulates opioid gating of GABA neurotransmission in the ventral pallidum.
        J Neurosci. 2014; 34: 1057-1066
        • Jabourian M.
        • Venance L.
        • Bourgoin S.
        • Ozon S.
        • Perez S.
        • Godeheu G.
        • et al.
        Functional mu opioid receptors are expressed in cholinergic interneurons of the rat dorsal striatum: Territorial specificity and diurnal variation.
        Eur J Neurosci. 2005; 21: 3301-3309
        • Svingos A.L.
        • Colago E.E.
        • Pickel V.M.
        Vesicular acetylcholine transporter in the rat nucleus accumbens shell: Subcellular distribution and association with mu-opioid receptors.
        Synapse. 2001; 40: 184-192
        • O’Donnell P.
        • Grace A.A.
        Synaptic interactions among excitatory afferents to nucleus accumbens neurons: Hippocampal gating of prefrontal cortical input.
        J Neurosci. 1995; 15: 3622-3639
        • Sora I.
        • Takahashi N.
        • Funada M.
        • Ujike H.
        • Revay R.S.
        • Donovan D.M.
        • et al.
        Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia.
        Proc Natl Acad Sci U S A. 1997; 94: 1544-1549
        • Pasternak G.W.
        Opiate pharmacology and relief of pain.
        J Clin Oncol. 2014; 32: 1655-1661
        • Navratilova E.
        • Morimura K.
        • Xie J.Y.
        • Atcherley C.W.
        • Ossipov M.H.
        • Porreca F.
        Positive emotions and brain reward circuits in chronic pain.
        J Comp Neurol. 2016; 524: 1646-1652
        • Lee M.
        • Manders T.R.
        • Eberle S.E.
        • Su C.
        • D’Amour J.
        • Yang R.
        • et al.
        Activation of corticostriatal circuitry relieves chronic neuropathic pain.
        J Neurosci. 2015; 35: 5247-5259
        • Frenois F.
        • Cador M.
        • Caille S.
        • Stinus L.
        • Le Moine C.
        Neural correlates of the motivational and somatic components of naloxone-precipitated morphine withdrawal.
        Eur J Neurosci. 2002; 16: 1377-1389
        • Williams J.T.
        • Christie M.J.
        • Manzoni O.
        Cellular and synaptic adaptations mediating opioid dependence.
        Physiol Rev. 2001; 81: 299-343
        • Zhu Y.
        • Wienecke C.F.
        • Nachtrab G.
        • Chen X.
        A thalamic input to the nucleus accumbens mediates opiate dependence.
        Nature. 2016; 530: 219-222
        • Leite-Morris K.A.
        • Fukudome E.Y.
        • Shoeb M.H.
        • Kaplan G.B.
        GABA(B) receptor activation in the ventral tegmental area inhibits the acquisition and expression of opiate-induced motor sensitization.
        J Pharmacol Exp Ther. 2004; 308: 667-678
        • Barghon R.
        • Protais P.
        • Colboc O.
        • Costentin J.
        Hypokinesia in mice and catalepsy in rats elicited by morphine associated with antidopaminergic agents, including atypical neuroleptics.
        Neurosci Lett. 1981; 27: 69-73
        • Kuribara H.
        Modification of morphine sensitization by opioid and dopamine receptor antagonists: evaluation by studying ambulation in mice.
        Eur J Pharmacol. 1995; 275: 251-258
        • Rodriguez-Arias M.
        • Broseta I.
        • Aguilar M.A.
        • Minarro J.
        Lack of specific effects of selective D(1) and D(2) dopamine antagonists vs. risperidone on morphine-induced hyperactivity.
        Pharmacol Biochem Behav. 2000; 66: 189-197
        • Becker A.
        • Grecksch G.
        • Brodemann R.
        • Kraus J.
        • Peters B.
        • Schroeder H.
        • et al.
        Morphine self-administration in mu-opioid receptor-deficient mice.
        Naunyn Schmiedebergs Arch Pharmacol. 2000; 361: 584-589
        • Sora I.
        • Elmer G.
        • Funada M.
        • Pieper J.
        • Li X.F.
        • Hall F.S.
        • Uhl G.R.
        Mu opiate receptor gene dose effects on different morphine actions: Evidence for differential in vivo mu receptor reserve.
        Neuropsychopharmacology. 2001; 25: 41-54
        • Bozarth M.A.
        • Wise R.A.
        Intracranial self-administration of morphine into the ventral tegmental area in rats.
        Life Sci. 1981; 28: 551-555
        • Devine D.P.
        • Wise R.A.
        Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of rats.
        J Neurosci. 1994; 14: 1978-1984
        • Fields H.L.
        • Hjelmstad G.O.
        • Margolis E.B.
        • Nicola S.M.
        Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement.
        Annu Rev Neurosci. 2007; 30: 289-316
        • Crittenden J.R.
        • Tillberg P.W.
        • Riad M.H.
        • Shima Y.
        • Gerfen C.R.
        • Curry J.
        • et al.
        Striosome-dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons.
        Proc Natl Acad Sci U S A. 2016; 113: 11318-11323
        • Ikemoto S.
        Brain reward circuitry beyond the mesolimbic dopamine system: A neurobiological theory.
        Neurosci Biobehav Rev. 2010; 35: 129-150
        • Berridge K.C.
        • Robinson T.E.
        • Aldridge J.W.
        Dissecting components of reward: ’Liking’, ’wanting’, and learning.
        Curr Opin Pharmacol. 2009; 9: 65-73
        • Olmstead M.C.
        • Ouagazzal A.M.
        • Kieffer B.L.
        Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task.
        PLoS One. 2009; 4: e4410

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        Biological PsychiatryVol. 84Issue 11
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          Erratum to: “Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food” (Biol Psychiatry 2017; 81:778–788); https://doi.org/10.1016/j.biopsych.2016.12.022 .
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