Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

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

  • Author(s): 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
  • et al.

Published Web Location

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View