@article{cfcf899aa8434011b989f2c01f23b22f,
title = "An endogenous opioid circuit determines state-dependent reward consumption",
abstract = "µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1–3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR–Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward.",
author = "Castro, {Daniel C.} and Oswell, {Corinna S.} and Zhang, {Eric T.} and Pedersen, {Christian E.} and Piantadosi, {Sean C.} and Rossi, {Mark A.} and Hunker, {Avery C.} and Anthony Guglin and Mor{\'o}n, {Jose A.} and Zweifel, {Larry S.} and Stuber, {Garret D.} and Bruchas, {Michael R.}",
note = "Funding Information: Acknowledgements We thank L. Lawson, D. Blumenthal, M. Chung, T. Hobbs and C. Pizzano for animal colony maintenance; the Bruchas laboratory, Stuber laboratory and multiple trainees and faculty within the NAPE Center for helpful discussions; B. Kieffer for the Oprm1fl/fl mice; and G. Scherrer for the Penk-Cre mice. D.C.C. was funded by NIH grants NS007205, DA043999, DA049862 and DA051489. C.E.P. was funded by NIH grant DA051124. M.A.R. was funded by NIH grant DK121883 and a NARSAD Young Investigator Award. J.A.M. was funded by NIH grants DA041781, DA042499 and DA045463. G.D.S. was funded by DA032750, DA038168 and DA048736. M.R.B. was funded by NIH grants R37DA033396 and R61DA051489 and the Mallinckrodt Endowed Professorship. M.R.B., G.D.S. and L.S.Z. were funded by NIH grant P30DA048736. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = oct,
day = "28",
doi = "10.1038/s41586-021-04013-0",
language = "English (US)",
volume = "598",
pages = "646--651",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7882",
}