@article{52a9269ac1a4454b916ca263d94abde8,
title = "Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine",
abstract = "Opioid receptors are expressed throughout the brain and play a major role in regulating striatal dopamine (DA) release. Clinical studies have shown that naloxone (NAL, a nonspecific opioid antagonist) in individuals with opioid use disorder and morphine (MRP, a nonspecific opioid agonist) in healthy controls, resulted in DA release in the dorsal and ventral striatum, respectively. It is not known whether the underlying patterns of striatal DA release are associated with the striatal distribution of opioid receptors. We leveraged previously published PET datasets (collected in independent cohorts) to study the brain-wide distribution of opioid receptors and to compare striatal opioid receptor availability with striatal DA release patterns. We identified three major gray matter segments based on availability maps of DA and opioid receptors: striatum, and primary and secondary opioid segments with high and intermediate opioid receptor availability, respectively. Patterns of DA release induced by NAL and MRP were inversely associated and correlated with kappa (NAL: r(68) = −0.81, MRP: r(68) = 0.54), and mu (NAL: r(68) = −0.62, MRP: r(68) = 0.46) opioid receptor availability. Kappa opioid receptor availability accounted for a unique part of variance in NAL- and MRP-DA release patterns (ΔR2 >0.14, p <.0001). In sum, distributions of opioid receptors distinguished major cortical and subcortical regions. Patterns of NAL- and MRP-induced DA release had inverse associations with striatal opioid receptor availability. Our approach provides a pattern-based characterization of drug-induced DA targets and is relevant for modeling the role of opioid receptors in modulating striatal DA release.",
keywords = "dopamine, k-means, morphine, naloxone, opioid receptors, positron emission tomography (PET), striatum",
author = "Ehsan Shokri-Kojori and Mika Naganawa and Ramchandani, {Vijay A.} and Wong, {Dean F.} and Wang, {Gene Jack} and Volkow, {Nora D.}",
note = "Funding Information: The authors thank Hiroto Kuwabara for modeling the MOR and DOR data and Mary McCaul R01AA11855 (PI: McCaul) and Elise Weerts for providing the DOR data. The authors thank Henry Huang and Richard Carson for providing the KOR dataset. The authors thank Christopher Wong for assistance with behavioral and imaging data. The authors thank Hugo Tejeda, Sunny Kim, Min Guo, and Abolghasem Bakhoda for helpful discussions. The authors thank Ayon Nandi for assistance with PET data at JHU. The authors thank Primavera Spagnolo, Melanie Schwandt, Nancy Diazgranados, and Markus Heilig for MRP study support and Peter Herscovitch and Shielah Conant for assistance with PET data at the NIH. The authors thank members of Laboratory of Neuroimaging at the NIAAA for their support. This work was supported by National Institute on Alcohol Abuse and Alcoholism intramural research program (Grant Y1AA3009). Funding Information: The authors thank Hiroto Kuwabara for modeling the MOR and DOR data and Mary McCaul R01AA11855 (PI: McCaul) and Elise Weerts for providing the DOR data. The authors thank Henry Huang and Richard Carson for providing the KOR dataset. The authors thank Christopher Wong for assistance with behavioral and imaging data. The authors thank Hugo Tejeda, Sunny Kim, Min Guo, and Abolghasem Bakhoda for helpful discussions. The authors thank Ayon Nandi for assistance with PET data at JHU. The authors thank Primavera Spagnolo, Melanie Schwandt, Nancy Diazgranados, and Markus Heilig for MRP study support and Peter Herscovitch and Shielah Conant for assistance with PET data at the NIH. The authors thank members of Laboratory of Neuroimaging at the NIAAA for their support. This work was supported by National Institute on Alcohol Abuse and Alcoholism intramural research program (Grant Y1AA3009). Publisher Copyright: {\textcopyright} 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.",
year = "2022",
month = mar,
doi = "10.1002/hbm.25733",
language = "English",
volume = "43",
pages = "1419--1430",
journal = "Human Brain Mapping",
issn = "1065-9471",
number = "4",
}