Targeted expression of µ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.

Cui, Yijun; Ostlund, Sean B; James, Alex S; Park, Chang Sin; Ge, Weihong; Roberts, Kristofer W; Mittal, Nitish; Murphy, Niall P; Cepeda, Carlos; Kieffer, Brigitte L; Levine, Michael S; Jentsch, James David; Walwyn, Wendy M; Sun, Yi E; Evans, Christopher J; Maidment, Nigel T; Yang, X William

Cui, Yijun; Ostlund, Sean B; James, Alex S; Park, Chang Sin; Ge, Weihong; Roberts, Kristofer W; Mittal, Nitish; Murphy, Niall P; Cepeda, Carlos; Kieffer, Brigitte L; Levine, Michael S; Jentsch, James David; Walwyn, Wendy M; Sun, Yi E; Evans, Christopher J; Maidment, Nigel T; Yang, X William.

Affiliation

Cui Y; 1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [3] Brain Re
Ostlund SB; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
James AS; Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA.
Park CS; 1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [3] Brain Re
Ge W; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [3] Intellectual Development and Disabilities Research Center, Semel
Roberts KW; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Mittal N; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Murphy NP; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Cepeda C; 1] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [2] David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [3] Intellectual Development and Disabilities Research Center, Semel Institute for Neuroscience,
Kieffer BL; Institut de Génétique et Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS)/Institut National de la Santé et de la Recherche Médicale (INSERM)/Université de Strasbourg (UdS), Illkirch, France.
Levine MS; 1] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [2] David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [3] Intellectual Development and Disabilities Research Center, Semel Institute for Neuroscience,
Jentsch JD; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] Department of Psychology, University of California, Los Angeles, Los Ang
Walwyn WM; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Sun YE; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [3] Intellectual Development and Disabilities Research Center, Semel
Evans CJ; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Maidment NT; 1] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [2] Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA. [3] David Geffen School of Medicine, University of California, Los Angeles,
Yang XW; 1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA. [3] Brain Re

Nat Neurosci ; 17(2): 254-61, 2014 Feb.

Article in En | MEDLINE | ID: mdl-24413699

ABSTRACT

ABSTRACT

µ-opioid receptors (MORs) are necessary for the analgesic and addictive effects of opioids such as morphine, but the MOR-expressing neuronal populations that mediate the distinct opiate effects remain elusive. Here we devised a new conditional bacterial artificial chromosome rescue strategy to show, in mice, that targeted MOR expression in a subpopulation of striatal direct-pathway neurons enriched in the striosome and nucleus accumbens, in an otherwise MOR-null background, restores opiate reward and opiate-induced striatal dopamine release and partially restores motivation to self administer an opiate. However, these mice lack opiate analgesia or withdrawal. We used Cre-mediated deletion of the rescued MOR transgene to establish that expression of the MOR transgene in the striatum, rather than in extrastriatal sites, is needed for the restoration of opiate reward. Our study demonstrates that a subpopulation of striatal direct-pathway neurons is sufficient to support opiate reward-driven behaviors and provides a new intersectional genetic approach to dissecting neurocircuit-specific gene function in vivo.

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Reward / Receptors, Opioid, mu / Corpus Striatum / Neural Pathways / Neurons Limits: Animals Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2014 Document type: Article

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