Understanding opioid reward

Fields, Howard L.; Margolis, Elyssa B.

doi:10.1016/j.tins.2015.01.002

Cited by 433Neurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal PhysiologyNeuroscience and Neuropharmacology Research

Understanding opioid reward

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Fields, Howard L., Margolis, Elyssa B.·2015·Trends in Neurosciences

DOI 10.1016/j.tins.2015.01.002PMC PMC4385443

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Abstract

Opioids are the most potent analgesics in clinical use; however, their powerful rewarding properties can lead to addiction. The scientific challenge is to retain analgesic potency while limiting the development of tolerance, dependence, and addiction. Both rewarding and analgesic actions of opioids depend upon actions at the mu opioid (MOP) receptor. Systemic opioid reward requires MOP receptor function in the midbrain ventral tegmental area (VTA) which contains dopaminergic neurons. VTA dopaminergic neurons are implicated in various aspects of reward including reward prediction error, working memory, and incentive salience. It is now clear that subsets of VTA neurons have different pharmacological properties and participate in separate circuits. The degree to which MOP receptor agonists act on different VTA circuits depends upon the behavioral state of the animal, which can be altered by manipulations such as food deprivation or prior exposure to MOP receptor agonists.

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Other neuromodulators, such as opioids, are more intrinsic to reward than dopamine.
“Other neuromodulators, such as opioids, seem to be more intrinsic to reward in that regard (e.g. Fields and Margolis, 2015).”
From The theory of constructed emotion: an active inference account of interoception and categorization (2016) · cites this paper as Fields and Margolis, 2015
The section “Both dopaminergic and non-dopaminergic circuits can contribute to VTA opioid reward” says opioid reward can occur without normal dopamine function. That supports a narrower point about opioid reward, but the paper does not establish that opioids are generally more intrinsic to reward than dopamine; it also describes dopamine’s role as dependent on the animal’s state. Page numbers are unavailable in our copy. (LLM, conf=0.83)
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Research works printed but not linked: 2

[37]Carr DB Sesack SR GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex Synapse 2000 38 114 123 11018785
[123]Hamilton ME Overflow of dopamine and cholecystokinin in rat nucleus accumbens in response to acute drug administration Synapse 2000 38 238 242 11020226

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Authors: Fields, H. L., & Margolis, E. B.
Affiliations: University of California, San Francisco (US)
Corresponding author: Fields, Howard L.
ORCID: Fields, Howard L.
Margolis, Elyssa B.
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 2015-04
Volume: 38
Issue: 4
Pages: 217-225
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/j.tins.2015.01.002
PMC: PMC4385443
OpenAlex: W2035419353
Cited by: 432
References: 131
Citations by year: 2026: 23 · 2025: 33 · 2024: 22 · 2023: 36 · 2022: 37 · 2021: 93 · 2020: 43 · 2019: 50 · 2018: 31 · 2017: 26 · 2016: 23 · 2015: 15
FWCI: 3.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute on Drug Abuse (R01DA029776)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: opioid reward, mu-opioid receptor, ventral tegmental area, dopaminergic neurons, opioid use disorder, analgesia, reward prediction error, incentive salience, working memory, behavioral state, food deprivation, opioid tolerance
MeSH terms: Analgesics, Opioid, Animals, Humans, Receptors, Opioid, Reinforcement, Psychology, Reward, Receptors, Opioid, mu, Ventral Tegmental Area, Dopaminergic Neurons

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