Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Blockade of endogenous opioid neurotransmission enhances acquisition of conditioned fear in humans.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Neuroimaging of the periaqueductal gray: state of the field.NeuroImage · 2012Pooled it
- Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain.NeuroImage · 2011Pooled it
- Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans.Hormones and behavior · 2018Trial
- Endogenous opioids regulate social threat learning in humans.Nature communications · 2017Trial
- Trial
- Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain.Proceedings of the National Academy of Sciences of the United States of America · 2015Trial
- Trial
- Pleasure-related analgesia activates opioid-insensitive circuits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Trial
- Anterior insula integrates information about salience into perceptual decisions about pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Trial
- Trial
- Naltrexone during pain conditioning: A double-blind placebo-controlled experimental trial.Molecular painTrial
- Endogenous opioid system modulates proximal and distal threat signals in the human brain.Molecular psychiatry · 2026Article
- Oxytocin and opioid antagonists: A dual approach to improving social behavior.Annals of the New York Academy of Sciences · 2025Review
- Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.Medical gas research · 2025Review
- Opioid Regulation of Social Homeostasis: Connecting Loneliness to Addiction.Biological psychiatry · 2025Review
- Convergent state-control of endogenous opioid analgesia.bioRxiv : the preprint server for biology · 2025Article
- Reward processes in extinction learning and applications to exposure therapy.Journal of anxiety disorders · 2024Review
- The Nocebo Effect.Annual review of pharmacology and toxicology · 2024Review
- Pain, Fear, Anxiety, and Stress: Relations to the Endogenous Opioid System.Advances in neurobiology · 2024Article
- Transforming experiences: Neurobiology of memory updating/editing.Frontiers in systems neuroscience · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endogenous opioid system is involved in fear learning in rodents, as opioid agonists attenuate and opioid antagonists facilitate the acquisition of conditioned fear. It has been suggested that an opioidergic signal, which is engaged through conditioning and acts inhibitory on unconditioned stimulus input, is the source of these effects. To clarify whether blockade of endogenous opioid neurotransmission enhances acquisition of conditioned fear in humans, and to elucidate the neural underpinnings of such an effect, we used functional magnetic resonance imaging in combination with behavioral recordings and a double-blind pharmacological intervention. All subjects underwent the same classical fear-conditioning paradigm, but subjects in the experimental group received the opioid antagonist naloxone before and during the experiment, in contrast to subjects in the control group, who received saline. Blocking endogenous opioid neurotransmission with naloxone led to more sustained responses to the unconditioned stimulus across trials, evident in both behavioral and blood oxygen level-dependent responses in pain responsive cortical regions. This effect was likely caused by naloxone blocking conditioned responses in a pain-inhibitory circuit involving opioid-rich areas such as the rostral anterior cingulate cortex, amygdala, and periaqueductal gray. Most importantly, naloxone enhanced the acquisition of fear on the behavioral level and changed the activation profile of the amygdala: whereas the control group showed rapidly decaying conditioned responses across trials, the naloxone group showed sustained conditioned responses in the amygdala. Together, these results demonstrate that in humans the endogenous opioid system has an inhibitory role in the acquisition of fear.
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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.