ArticleBritish journal of pharmacology2014
Analgesic tolerance to morphine is regulated by PPARγ.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users.Physiology & behavior · 2016Trial
- The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.Journal of psychoactive drugsTrial
- Large-scale behavioral characterization of oxycodone self-administration in heterogeneous stock rats reveals initial analgesic effects are associated with addiction-like behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Perinatal fentanyl exposure drives enduring addiction risk and central amygdala gene dysregulation.Neuropharmacology · 2025Article
- β-caryophyllene inhibits heroin self-administration, but does not alter opioid-induced antinociception in rodents.Neuropharmacology · 2024Article
- Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis.The Korean journal of pain · 2024Article
- Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives.Molecular and cellular biochemistry · 2024Review
- Promising immunomodulators for management of substance and alcohol use disorders.Expert opinion on pharmacotherapy · 2024Review
- Neuroimmune modulators as novel pharmacotherapies for substance use disorders.Brain, behavior, & immunity - health · 2024Article
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Strain and sex-related behavioral variability of oxycodone dependence in rats.Neuropharmacology · 2023Article
- Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats.International journal of molecular sciences · 2023Article
- An updated review on phytochemistry and molecular targets ofFrontiers in pharmacology · 2023Review
- Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway.Molecular medicine reports · 2022Article
- The PPARγ agonist pioglitazone produces a female-predominant inhibition of hyperalgesia associated with surgical incision, peripheral nerve injury, and painful diabetic neuropathy.Neuropharmacology · 2022Article
- Morphine enhances LPS-induced macrophage apoptosis through a PPARγ-dependent mechanism.Experimental and therapeutic medicine · 2021Article
- Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids.Journal of neuroinflammation · 2020Article
- Further evidence for the involvement of the PPARγ system on alcohol intake and sensitivity in rodents.Psychopharmacology · 2020Article
- Review
- Inhibition of fatty acid amide hydrolase in the CNS prevents and reverses morphine tolerance in male and female mice.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeOpioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice. EXPERIMENTAL APPROACH: We monitored analgesia on alternate days using the tail immersion test. KEY
resultsDaily administration of morphine (30 mg·kg(-1) , bid) resulted in the rapid development of tolerance to thermal analgesia. Co-administration of pioglitazone (10 and 30 mg·kg(-1) , bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW-9662 (5 mg·kg(-1) , bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW-9662 and a lower dose of morphine (15 mg·kg(-1) , bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild-type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance. CONCLUSIONS AND IMPLICATIONS: Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse.
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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.