ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Evidence that behavioral phenotypes of morphine in β-arr2-/- mice are due to the unmasking of JNK signaling.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- An Overview of Recent Developments in the Management of Burn Injuries.International journal of molecular sciences · 2023Review
- Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine.Biomolecules · 2023Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Functional Selectivity Does Not Predict Antinociceptive/Locomotor Impairing Potencies of NOP Receptor Agonists.Frontiers in neuroscience · 2021Article
- Loss of β-arrestin2 in D2 cells alters neuronal excitability in the nucleus accumbens and behavioral responses to psychostimulants and opioids.Addiction biology · 2020Article
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
- Toward Directing Opioid Receptor Signaling to Refine Opioid Therapeutics.Biological psychiatry · 2020Review
- Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits.The pharmacogenomics journal · 2019Article
- Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment.Neuroscience and biobehavioral reviews · 2019Review
- Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src.Scientific reports · 2017Article
- Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.Trends in pharmacological sciences · 2016Review
- β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.Cell death and differentiation · 2016Article
- Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestin-dependent and independent mechanisms.Cellular signalling · 2015Article
- Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.Molecular pain · 2015Article
- β-Arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but does not affect opioid-withdrawal-related adaptations in single PAG neurons.British journal of pharmacology · 2015Article
- Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors.British journal of pharmacology · 2015Article
- Change in functional selectivity of morphine with the development of antinociceptive tolerance.British journal of pharmacology · 2015Article
- The μ-opioid receptor: an electrophysiologist's perspective from the sharp end.British journal of pharmacology · 2015Review
- Opioid receptor desensitization: mechanisms and its link to tolerance.Frontiers in pharmacology · 2014Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The altered behavioral effects of morphine, but not most other mu agonists, in mice lacking β-arrestin 2, suggest that this scaffolding protein regulates the signaling cascade of this commonly used analgesic. One of the cascades that could be regulated by β-arrestin 2 is cJun-N-terminal kinase (JNK), which binds with β-arrestin 2 and modulates the analgesic effects of morphine. Using neurons lacking β-arrestin 2 (β-arr2-/-) to examine this interaction, we found that β-arr2-/- neurons show altered intracellular distribution of JNK and cJun, and that morphine, but not fentanyl, increased the nuclear localization of the phosphorylated, therefore activated, form of cJun, a JNK target in dorsal root ganglia neurons. This suggests that deleting β-arrestin 2 affects the JNK cascade. We therefore examined whether some of the behavioral phenotypes of mice lacking β-arrestin 2 could be a result of altered JNK signaling. Indeed, two different JNK inhibitors reversed the enhanced analgesic effect of morphine, a known phenotype of β-arr2-/- mice, to +/+ levels. Both the reduced locomotor effect of morphine and the psychomotor sensitization to repeated morphine administration in β-arr2-/- mice were also returned to +/+ levels by inhibiting JNK. In contrast, the behavioral effects of fentanyl were neither genotype-dependent nor affected by JNK inhibition. Furthermore, a PKC inhibitor had a similar effect as inhibiting JNK in reducing the enhanced analgesic effect of morphine in β-arr2-/- mice to +/+ levels. In summary, removing β-arrestin 2 reveals mu receptor activation of the JNK cascade in a ligand-specific manner explaining several behavioral phenotypes of β-arr2-/- mice.
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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.