Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.
Title | Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Cui 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 |
Journal | Nat Neurosci |
Volume | 17 |
Issue | 2 |
Pagination | 254-61 |
Date Published | 2014 Feb |
ISSN | 1546-1726 |
Keywords | Analysis 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. |
DOI | 10.1038/nn.3622 |
Alternate Journal | Nat. Neurosci. |
PubMed ID | 24413699 |
PubMed Central ID | PMC4008330 |
Grant List | AI-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 |