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)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-EXL-T (02))
Program Officer
Pollock, Jonathan D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Bakhurin, Konstantin I; Goudar, Vishwa; Shobe, Justin L et al. (2017) Differential Encoding of Time by Prefrontal and Striatal Network Dynamics. J Neurosci 37:854-870
Ehrlich, Aliza T; Semache, Meriem; Bailly, Julie et al. (2017) Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing. Brain Struct Funct :
Lalanne, L; Ayranci, G; Filliol, D et al. (2017) Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence. Addict Biol 22:1010-1021
Dagnew, Robel; Lin, Yin-Ying; Agatep, Jerikko et al. (2017) CerebraLux: a low-cost, open-source, wireless probe for optogenetic stimulation. Neurophotonics 4:045001
Boulos, Laura-Joy; Darcq, Emmanuel; Kieffer, Brigitte Lina (2017) Translating the Habenula-From Rodents to Humans. Biol Psychiatry 81:296-305
Ben Hamida, Sami; Boulos, Laura-Joy; McNicholas, Michael et al. (2017) Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking. Addict Biol :
Charbogne, Pauline; Gardon, Olivier; Martín-García, Elena et al. (2017) Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food. Biol Psychiatry 81:778-788
Pradhan, Amynah A; Perroy, Julie; Walwyn, Wendy M et al. (2016) Agonist-Specific Recruitment of Arrestin Isoforms Differentially Modify Delta Opioid Receptor Function. J Neurosci 36:3541-51
Cahill, Catherine M; Walwyn, Wendy; Taylor, Anna M W et al. (2016) Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation. Trends Pharmacol Sci 37:963-976
Storey, Granville P; Gonzalez-Fernandez, Gabriel; Bamford, Ian J et al. (2016) Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice(1,2,3). eNeuro 3:

Showing the most recent 10 out of 111 publications