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- Title
Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.
- Authors
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
- 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.
- Subjects
OPIOID receptors; ANALGESICS; NEURONS; MORPHINE; TRANSGENES; NEURAL circuitry; DOPAMINE
- Publication
Nature Neuroscience, 2014, Vol 17, Issue 2, p254
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.3622