ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Contribution of adenylyl cyclase modulation of pre- and postsynaptic GABA neurotransmission to morphine antinociception and tolerance.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 44 citations in OpenAlex.
- GABAergic neurons in the ventrolateral periaqueductal gray mediate fentanyl withdrawal and self-administration in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The Impact of Levetiracetam on Various Symptoms of Morphine Dependence in Mice.Life (Basel, Switzerland) · 2026Article
- A neural circuit for sex-dependent conditioned pain hypersensitivity in mice.Nature communications · 2025Article
- A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy.Annual review of physiology · 2024Review
- Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Brain transcriptome of gobies inhabiting natural COEvolutionary applications · 2023Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.Journal of neuroinflammation · 2022Article
- Comprehensive Signaling Profiles Reveal Unsuspected Functional Selectivity of δ-Opioid Receptor Agonists and Allow the Identification of Ligands with the Greatest Potential for Inducing Cyclase Superactivation.ACS pharmacology & translational science · 2021Article
- Mice Expressing Regulators of G protein Signaling-insensitive Gαo Define Roles ofMolecular pharmacology · 2021Article
- Addressing opioid tolerance and opioid-induced hypersensitivity: Recent developments and future therapeutic strategies.Pharmacology research & perspectives · 2021Review
- Spinal heat shock protein 27 participates in PDGFRβ-mediated morphine tolerance through PI3K/Akt and p38 MAPK signalling pathways.British journal of pharmacology · 2020Article
- Endogenous opioid peptides in the descending pain modulatory circuit.Neuropharmacology · 2020Review
- Opioid-Induced Signaling and Antinociception Are Modulated by the Recently Deorphanized Receptor, GPR171.The Journal of pharmacology and experimental therapeutics · 2019Article
- Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.Peptides · 2019Review
- Inhibition of GABAergic Neurons and Excitation of Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray Participate in Electroacupuncture Analgesia Mediated by Cannabinoid Receptor.Frontiers in neuroscience · 2019Article
- Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Periaqueductal Gray Glutamatergic Transmission Governs Chronic Stress-Induced Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- The Contribution of the Descending Pain Modulatory Pathway in Opioid Tolerance.Frontiers in neuroscience · 2018Article
- Chronic morphine reduces the readily releasable pool of GABA, a presynaptic mechanism of opioid tolerance.The Journal of physiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Opioid inhibition of presynaptic GABA release in the ventrolateral periaqueductal gray (vlPAG) activates the descending antinociception pathway. Tolerance to repeated opioid administration is associated with upregulation of adenylyl cyclase activity. The objective of these studies was to test the hypothesis that adenylyl cyclase contributes to opioid tolerance by modulating GABA neurotransmission. Repeated microinjections of morphine or the adenylyl cyclase activator NKH477 into the vlPAG decreased morphine antinociception as would be expected with the development of tolerance. Conversely, microinjection of the adenylyl cyclase inhibitor SQ22536 reversed both the development and expression of morphine tolerance. These behavioral results indicate that morphine tolerance is dependent on adenylyl cyclase activation. Electrophysiological experiments revealed that acute activation of adenylyl cyclase with forskolin increased the frequency of presynaptic GABA release. However, recordings from rats treated with repeated morphine administration did not exhibit increased basal miniature inhibitory postsynaptic current (mIPSC) frequency but showed a decrease in mean amplitude of mIPSCs indicating that repeated morphine administration modulates postsynaptic GABAA receptors without affecting the probability of presynaptic GABA release. SQ22536 reversed this change in mIPSC amplitude and inhibited mIPSC frequency selectively in morphine tolerant rats. Repeated morphine or NKH477 administration also decreased antinociception induced by microinjection of the GABAA receptor antagonist bicuculline, further demonstrating changes in GABA neurotransmission with morphine tolerance. These results show that the upregulation of adenylyl cyclase caused by repeated vlPAG morphine administration produces antinociceptive tolerance by modulating both pre- and postsynaptic GABA neurotransmission.
Indexed as
Identifiers
What OpenQuestion holds
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.