ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
Reduced nucleus accumbens enkephalins underlie vulnerability to social defeat stress.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed.
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Rapid-Onset Therapeutic Effects of Delta Opioid Receptor Agonists on Depression-Like Behaviors Induced by Chronic Social Defeat Stress.Neuropsychopharmacology reports · 2025Article
- Unveiling Dopamine and Met-Enkephalin Dynamics: Simultaneous Co-Detection in Rat Striatum.Analytical chemistry · 2025Article
- Sexually Dimorphic Cellular Architecture and Neural Circuity of ovBNST Proenkephalin Neurons.Neuroscience bulletin · 2025Article
- Highly sensitive in vivo detection of dynamic changes in enkephalins following acute stress in mice.eLife · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Opioid receptor signaling throughout ontogeny: Shaping neural and behavioral trajectories.Neuroscience and biobehavioral reviews · 2025Review
- Stress-Induced Changes in the Endogenous Opioid System Cause Dysfunction of Pain and Emotion Regulation.International journal of molecular sciences · 2023Review
- Maturation of nucleus accumbens synaptic transmission signals a critical period for the rescue of social deficits in a mouse model of autism spectrum disorder.Molecular brain · 2023Article
- Protective Role and Functional Engineering of Neuropeptides in Depression and Anxiety: An Overview.Bioengineering (Basel, Switzerland) · 2023Review
- Molecular, Circuit, and Stress Response Characterization of Ventral Pallidum Npas1-Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Contribution of the Opioid System to the Antidepressant Effects of Fluoxetine.Biological psychiatry · 2022Article
- Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.Cell reports · 2022Article
- Mediation of the behavioral effects of ketamine and (2R,6R)-hydroxynorketamine in mice by kappa opioid receptors.Psychopharmacology · 2022Article
- Angiotensin-converting enzyme gates brain circuit-specific plasticity via an endogenous opioid.Science (New York, N.Y.) · 2022Article
- Resilience to the effects of social stress on vulnerability to developing drug addiction.World journal of psychiatry · 2022Review
- Environmental Contributions to Anhedonia.Current topics in behavioral neurosciences · 2022Review
- Nucleus Accumbens Medium Spiny Neuron Subtypes Differentially Regulate Stress-Associated Alterations in Sleep Architecture.Biological psychiatry · 2021Article
- Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat stress.Psychopharmacology · 2021Article
- Harnessing the Neurobiology of Resilience to Protect the Mental Well-Being of Healthcare Workers During the COVID-19 Pandemic.Frontiers in psychology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Enkephalins, endogenous ligands for delta opioid receptors (DORs), are highly enriched in the nucleus accumbens (NAc). They are implicated in depression but their role in the NAc, a critical brain region for motivated behavior, is not fully investigated. To provide insight into enkephalin function we used a chronic social defeat stress paradigm, where animals are either categorized as susceptible or resilient to stress based on their performance in a social interaction test. Compared to controls, susceptible animals showed reduced enkephalin levels in the NAc. Such decrease in enkephalin levels is not due to a change in mRNA of its precursor protein, proenkephalin, in susceptible mice but is consistent with increased mRNA levels of enkephalinases in the NAc of susceptible animals. Systemic administration of enkephalinase inhibitors or NAc infusion of the DOR agonist, SNC80, caused a resilient outcome to CSDS. Both treatments increased phosphorylation of ERK, which was downregulated by social defeat stress. To further validate these results, we also used Q175 knock-in mice, an animal model of Huntington's disease in which enkephalin levels are reduced in striatum and comorbidity with mood disorders is common. Consistent with data in wild-type mice, Q175 animals showed reduced enkephalin levels in the NAc and enhanced susceptibility to a social defeat stress. Overall, our data implicate that depression-like behavior induced by social defeat stress arises from disrupted DOR signaling resulting from lowered levels of enkephalins, which is partly mediated through elevated expression of enkephalinases.
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.