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

TitleTargeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.
Publication TypeJournal Article
Year of Publication2014
AuthorsCui Y, Ostlund SB, James AS, Park CSin, Ge W, Roberts KW, Mittal N, Murphy NP, Cepeda C, Kieffer BL, Levine MS, Jentsch JDavid, Walwyn WM, Sun YE, Evans CJ, Maidment NT, X Yang W
JournalNat Neurosci
Volume17
Issue2
Pagination254-61
Date Published2014 Feb
ISSN1546-1726
KeywordsAnalysis of Variance, Animals, Conditioning, Operant, Corpus Striatum, Disease Models, Animal, Dopamine, Enkephalins, Exploratory Behavior, Flow Cytometry, Green Fluorescent Proteins, Mice, Mice, Transgenic, Microdialysis, Morphine, Naloxone, Narcotic Antagonists, Narcotics, Neural Pathways, Neurons, Pain, Pain Measurement, Protein Precursors, Receptors, Opioid, mu, Reward, Substance Withdrawal Syndrome
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.

DOI10.1038/nn.3622
Alternate JournalNat. Neurosci.
PubMed ID24413699
PubMed Central IDPMC4008330
Grant ListAI-28697 / AI / NIAID NIH HHS / United States
CA-16042 / CA / NCI NIH HHS / United States
P30HD004612 / HD / NICHD NIH HHS / United States
P50 DA005010 / DA / NIDA NIH HHS / United States
P50 DA005010 / DA / NIDA NIH HHS / United States
R01 DA029035 / DA / NIDA NIH HHS / United States
R01DA029035 / DA / NIDA NIH HHS / United States
T32 DA024635 / DA / NIDA NIH HHS / United States

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