Mu-opioid receptors are therapeutic targets for many addictive disorders since they are key components for mediating the rewarding effects of opiates, nicotine, cannabinoids, alcohol and food. The renewal of the UCLA Center for Opioid Receptors and Drugs of Abuse (CSORDA) will focus on the circuitry and cell-specific adaptations underlying addiction-related behaviors mediated by mu opioid receptors. The center will investigate hedonic control and reinforcement learning as well as dysphoria and relapse following abstinence of both opiate drugs and substances reliant on endogenous opioid circuitry to elicit reward. The research plan will build upon progress during the past funding period by incorporating several CSORDA-developed innovative genetic mouse models that selectively lack, or selectively rescue, mu-receptors in discrete cell-types and brain regions, and knock-in mice expressing fluorescently labeled mu receptors. CSORDA advances in instrumental behavior, including the measurement of "liking" and "wanting", self-administration of opioids, as well as models of dysphoric states, will provide synergistic analysis of addictive behaviors mediated by specific mu opioid receptor circuits. Four Research Components are proposed that are highly interactive both thematically and technically and that use shared models and reagents. A principle focus will be the central roles played by mu-opioid receptors in striatal sub regions (striosome/patch and matrix) and neuron sub-populations in addiction-related behaviors, including the relationship to dopamine transmission, and cellular and molecular adaptations in response to opioids (Components I, III and IV). With evidence for dopamine-independent mechanisms for mu-mediated reward, the contribution of extrastriatal mu-opioid receptors will also be assessed (Components II, III and IV) with a specific focus on the habenular complex, where mu-opioid receptor expression is the highest in the CNS. The research will employ mouse genetics and behavioral analysis combined with electrophysiology, optogenetics, single cell transcript analysis and epigenetics. CSORDA will support an Epigenetic/Transcriptome Profiling Core, and an Animal Breeding Core supplying all CSORDA Components with mouse models and extending facilities into the research community. The Administrative Core and CSORDA Advisory board, consisting of Drs. Balleine, Bonci, Koob, Levitt, Nestler and Whybrow ex-officio, will provide programmatic oversight and coordinate training, outreach and a Pilot Program for the center.

Public Health Relevance

The mu-opioid receptor that mediates physiological and psychological effects of morphine and heroin also mediates the rewarding effects of alcohol, nicotine, cannabis and food. This proposal will identify the mu-opioid receptor brain circuits that contribute to different aspects of addictive behaviors with a view to developing therapeutic strategies for addiction and opioid-based pain treatments.

National Institute of Health (NIH)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZDA1)
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Pollock, Jonathan D
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University of California Los Angeles
Overall Medical
Los Angeles
United States
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Erbs, Eric; Faget, Lauren; Scherrer, Gregory et al. (2015) A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks. Brain Struct Funct 220:677-702
Wang, Nan; Gray, Michelle; Lu, Xiao-Hong et al. (2014) Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease. Nat Med 20:536-41
Wassum, Kate M; Greenfield, Venuz Y; Linker, Kay E et al. (2014) Inflated reward value in early opiate withdrawal. Addict Biol :
Ivanov, Iliyan; Liu, Xun; Clerkin, Suzanne et al. (2014) Methylphenidate and brain activity in a reward/conflict paradigm: role of the insula in task performance. Eur Neuropsychopharmacol 24:897-906
Tsoa, Rosemarie W; Coskun, Volkan; Ho, Chi K et al. (2014) Spatiotemporally different origins of NG2 progenitors produce cortical interneurons versus glia in the mammalian forebrain. Proc Natl Acad Sci U S A 111:7444-9
Taylor, Anna M W; Murphy, Niall P; Evans, Christopher J et al. (2014) Correlation between ventral striatal catecholamine content and nociceptive thresholds in neuropathic mice. J Pain 15:878-85
Ostlund, Sean B; Kosheleff, Alisa R; Maidment, Nigel T (2014) Differential effects of systemic cholinergic receptor blockade on Pavlovian incentive motivation and goal-directed action selection. Neuropsychopharmacology 39:1490-7
Becker, Jérôme A J; Clesse, Daniel; Spiegelhalter, Coralie et al. (2014) Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity. Neuropsychopharmacology 39:2049-60
Pradhan, Amynah A; Smith, Monique L; McGuire, Brenna et al. (2014) Characterization of a novel model of chronic migraine. Pain 155:269-74
Liu, Hailiang; Chen, Yongchang; Niu, Yuyu et al. (2014) TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys. Cell Stem Cell 14:323-8

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