Neural Systems Underlying Opiate Addiction
Open accessAbstract
Opiate addiction is a chronically relapsing disorder that is characterized by compulsive drug taking, an inability to limit intake, and bouts of intense drug craving that can be precipitated by the mere presence of people, places, or objects previously associated with drug use. Although knowledge of
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Opioids produce their analgesic and dependency-forming effects through agonism of opioid receptors, most importantly the MOR, with downstream effect on GABAergic and dopaminergic neurotransmission.
“Opioids produce their analgesic and dependency-forming effects through agonism of opioid receptors, and, most importantly, the MOR, with downstream effect on GABAergic and dopaminergic neurotransmission.2,19,20”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [19]
The “Systems involved in opiate self-administration” section says opiates bind opioid receptors, identifies MOR as critical to heroin and morphine reward, and describes MOR agonists affecting GABA neurons and dopamine release. It does not explain analgesia through that GABA–dopamine pathway; analgesia appears only in the title of a cited study in the References. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAt the cellular level tolerance occurs because of the drive to homeostatic balance, involving de-sensitisation and down-regulation of MORs, as well as modifications to the mu-signalosome, neuronal proteome, transcriptome and neuronal morphology, with consequent downstream effects on mesolimbic dopaminergic neurons.
“At the cellular level tolerance occurs because of the drive to homeostatic balance, 2 involving de-sensitisation and down-regulation of MORs, as well as modifications to the mu-signalosome, neuronal proteome, transcriptome and neuronal morphology, 20 with consequent downstream effects on mesolimbic dopaminergic neurons.19,20”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [19]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe ability of MOR antagonists to induce withdrawal symptoms in individuals with physiological opioid dependence supports the concept that withdrawal occurs because the raised homeostatic set-point registers reduced doses as under activation.
“This concept is supported by the ability of MOR antagonists to induce withdrawal symptoms in individuals with physiological opioid dependence. 19”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [19]
In “Neuroadaptations resulting from chronic opiate use” (page unavailable), the paper says opioid receptor antagonists produce withdrawal signs in morphine-dependent animals and attributes those effects to MOR antagonism. It does not establish the effect in human individuals or describe withdrawal in terms of a raised homeostatic set-point; the latter is the citing authors’ interpretation. (LLM, conf=0.86)
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“19,20 Withdrawal symptoms occur when opioids are reduced or stopped because the raised homeostatic set-point of the mu-opioid system registers reduced doses as ‘under activation’.”
- Authors
- De Vries, T. J., & Shippenberg, T. S.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-05-01
- Volume
- 22
- Issue
- 9
- Pages
- 3321-3325
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758389
- OpenAlex
- W2096140192
- Cited by
- 270
- References
- 69
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 5 · 2014: 11 · 2013: 16 · 2012: 15
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- opioid use disorder, neural systems, relapse, compulsive drug taking, drug craving, drug cues, opioid reward
- MeSH terms
- Adaptation, Physiological, Animals, Humans, Motivation, Opioid-Related Disorders, Narcotics, Nervous System, Neuropeptides, Recurrence, Stress, Physiological, Neurotransmitter Agents
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