ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. 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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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- The ventral hippocampus: computations, circuits and functions.Nature reviews. Neuroscience · 2026Review
- Article
- Multi-omics characterization of chronic social defeat stress recall-activated nuclei in Arc-GFP mice.Molecular psychiatry · 2026Article
- The multilevel exploration test, a novel paradigm to measure exploratory behavior in depression animal models and the involvement of the PL-ZI circuit.Acta pharmacologica Sinica · 2026Article
- Maternal Isocaloric Monosaccharide Diets Reorganize Dorsal-Ventral Hippocampal Maturation and Ventral Plasticity in Rat Offspring.Cellular and molecular neurobiology · 2026Article
- A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors.Translational psychiatry · 2026Article
- Adenosine A2A receptors in the nucleus accumbens regulate stress resilience and predict susceptibility to stress-induced affective disturbances.Purinergic signalling · 2026Article
- L-fucose administration ameliorates chronic social defeat stress-induced depressive-like behaviors by restoring GDP-fucose biosynthetic activation and core fucosylation.Frontiers in immunology · 2026Article
- Rapid-Onset Therapeutic Effects of Delta Opioid Receptor Agonists on Depression-Like Behaviors Induced by Chronic Social Defeat Stress.Neuropsychopharmacology reports · 2025Article
- Parental preconceptual α-cypermethrin exposure alters embryonic brain transcriptomics in mice: Implications for autism spectrum disorder and stress vulnerability.Neurotoxicology · 2025Article
- Ketamine Reverses Chronic Stress-Induced Behavioral Changes via the Expression of CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- An inverted U-shaped relationship between chronic stress and the motivation to expend effort for reward.Neurobiology of stress · 2025Article
- Reward integration in prefrontal-cortical and ventral-hippocampal nucleus accumbens inputs cooperatively modulates engagement.Nature communications · 2025Article
- Differential effects of chronic unpredictable stress on behavioral and molecular (cortisol and microglia-related neurotranscriptomic) responses in adult leopard (leo) zebrafish.Fish physiology and biochemistry · 2025Article
- Article
- Transcriptomic Evaluation of a Stress Vulnerability Network Using Single-Cell RNA Sequencing in Mouse Prefrontal Cortex.Biological psychiatry · 2024Article
- Transient impact of chronic social stress on effort-based reward motivation in non-food restricted mice: Involvement of corticosterone.Neurobiology of stress · 2024Article
- A Double Hit of Social and Economic Stress in Mice Precipitates Changes in Decision-Making Strategies.Biological psychiatry · 2024Article
- Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons.Nature communications · 2024Article
- Depression in adolescence and young adulthood: the difficulty to integrate motivational/emotional systems.Frontiers in psychology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.
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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.