ArticleAddiction biology2015
Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence-induced hyperalgesia.
Article in Addiction biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction.Alcohol (Fayetteville, N.Y.) · 2025Review
- Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.Research square · 2025Article
- Fixed-proportion mixtures with the α2-adrenergic agonist clonidine or lofexidine do not alter fentanyl self-administration in non-opioid-dependent male and female rats.The Journal of pharmacology and experimental therapeutics · 2025Article
- Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice.Psychopharmacology · 2025Article
- Region-specific neuroadaptations of CRF1 and CRF2 expression following heroin exposure in female rats.Pharmacology, biochemistry, and behavior · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Chronic inflammatory pain reduces fentanyl intake during early acquisition of fentanyl self-administration, but does not change motivation to take fentanyl in male and female rats.Pharmacology, biochemistry, and behavior · 2024Article
- Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models.Nature communications · 2024Article
- Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.Pharmacology, biochemistry, and behavior · 2024Article
- The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.The international journal of neuropsychopharmacology · 2023Article
- Opioid withdrawal: role in addiction and neural mechanisms.Psychopharmacology · 2023Review
- Sex-specific biobehavioral regulation of persistent inflammatory pain by alcohol.Alcohol, clinical & experimental research · 2023Article
- Chronic inflammatory pain promotes place preference for fentanyl in male rats but does not change fentanyl self-administration in male and female rats.Neuropharmacology · 2023Article
- Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers.Addiction neuroscience · 2023Article
- Corticotropin releasing factor and drug seeking in substance use disorders: Preclinical evidence and translational limitations.Addiction neuroscience · 2022Article
- The role of glucagon-like peptide 1 (GLP-1) in addictive disorders.British journal of pharmacology · 2022Review
- Anhedonia, Hyperkatifeia, and Negative Reinforcement in Substance Use Disorders.Current topics in behavioral neurosciences · 2022Review
- Effect of early life social adversity on drug abuse vulnerability: Focus on corticotropin-releasing factor and oxytocin.Neuropharmacology · 2021Review
- Tolerance to alcohol: A critical yet understudied factor in alcohol addiction.Pharmacology, biochemistry, and behavior · 2021Review
- κ-Opioid receptor antagonism reverses heroin withdrawal-induced hyperalgesia in male and female rats.Neurobiology of stress · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.
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Registered trials
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.