ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Interruption of continuous opioid exposure exacerbates drug-evoked adaptations in the mesolimbic dopamine system.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- Can the incentive-sensitization theory of addiction incorporate addiction to opioid drugs?Psychopharmacology · 2026Review
- Changes in perineuronal net and parvalbumin expression in the orbitofrontal cortex of male Wistar rats following repeated fentanyl administration.bioRxiv : the preprint server for biology · 2026Article
- Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia.Psychopharmacology · 2026Article
- Changes in perineuronal net and parvalbumin expression in the orbitofrontal cortex of male Wistar rats following repeated fentanyl administration.Frontiers in neuroscience · 2026Article
- Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia.bioRxiv : the preprint server for biology · 2025Article
- Cannabis use frequency is associated with emotion dysregulation among persons receiving long-term opioid therapy for chronic pain: A psychophysiological study.Drug and alcohol dependence · 2025Article
- Nonpharmacological and pharmacological influences on opioid effects: A review of clinical research findings.The Journal of pharmacology and experimental therapeutics · 2025Review
- Fiber Photometry Analysis of Spontaneous Dopamine Signals: TheACS chemical neuroscience · 2025Article
- Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind.Nature neuroscience · 2025Article
- Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms.Neuropharmacology · 2025Article
- Article
- Fiber photometry analysis of spontaneous dopamine signals: The z-scored data are not the data.bioRxiv : the preprint server for biology · 2025Article
- Generalized cue reactivity in rat dopamine neurons after opioids.Nature communications · 2025Article
- Profiling gene alterations in striatonigral neurons associated with incubation of methamphetamine craving by cholera toxin subunit B-based fluorescence-activated cell sorting.Frontiers in cellular neuroscience · 2025Article
- Morphine-Driven m6A Epitranscriptomic Neuroadaptations in Primary Cortical Cultures.Molecular neurobiology · 2024Article
- Sex differences in morphine sensitivity of neuroligin-3 knockout mice.Psychopharmacology · 2024Article
- An emerging multi-omic understanding of the genetics of opioid addiction.The Journal of clinical investigation · 2024Article
- The effects of different types of social interactions on the electrophysiology of neurons in the nucleus accumbens in rodents.Neuroscience and biobehavioral reviews · 2024Review
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.