ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
Ketamine Corrects Stress-Induced Cognitive Dysfunction through JAK2/STAT3 Signaling in the Orbitofrontal Cortex.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Traumatic stress recruits an excitatory orbitofrontal-amygdala pathway to drive maladaptive aggression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review.Research square · 2026Article
- Central medial and paraventricular thalamic afferents to the orbitofrontal cortex have differential effects on reversal learning.Neurobiology of stress · 2026Article
- Corticosterone effects induced by stress and immunity and inflammation: mechanisms of communication.Frontiers in endocrinology · 2025Review
- Effects of chronic stress on cognitive function - From neurobiology to intervention.Neurobiology of stress · 2024Review
- A novel framework for ketamine-assisted couple therapy.Frontiers in psychiatry · 2024Review
- Role of Orbitofrontal Cortex and Differential Effects of Acute and Chronic Stress on Motor Impulsivity Measured With 1-Choice Serial Reaction Time Test in Male Rats.The international journal of neuropsychopharmacology · 2022Article
- Nicotine Activating αMolecular neurobiology · 2022Article
- Roles of non-receptor tyrosine kinases in pathogenesis and treatment of depression.Journal of integrative neuroscience · 2022Review
- Prefrontal cortex and depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- A Simple Computational Approach to Identify Potential Drugs for Multiple Sclerosis and Cognitive Disorders from Expert Curated Resources.Methods in molecular biology (Clifton, N.J.) · 2022Article
- STAT3 in the dorsal raphe gates behavioural reactivity and regulates gene networks associated with psychopathology.Molecular psychiatry · 2021Article
- Optogenetically-induced long term depression in the rat orbitofrontal cortex ameliorates stress-induced reversal learning impairment.Neurobiology of stress · 2020Article
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression.Molecular brain · 2020Article
- Ciliary neurotrophic factor signaling in the rat orbitofrontal cortex ameliorates stress-induced deficits in reversal learning.Neuropharmacology · 2019Article
- Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants.Translational psychiatry · 2019Article
- In vivo electrophysiological recordings of the effects of antidepressant drugs.Experimental brain research · 2019Review
- Ketamine and Active Ketamine Metabolites Regulate STAT3 and the Type I Interferon Pathway in Human Microglia: Molecular Mechanisms Linked to the Antidepressant Effects of Ketamine.Frontiers in pharmacology · 2019Article
- Ketamine Corrects a Deficit in Reversal Learning Caused by Chronic Intermittent Cold Stress in Female Rats.The international journal of neuropsychopharmacology · 2018Article
- Prefrontal cortex executive processes affected by stress in health and disease.Progress in neuro-psychopharmacology & biological psychiatry · 2018Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Deficits in cognitive flexibility are prominent in stress-related psychiatric disorders, including depression. Ketamine has rapid antidepressant efficacy, but it is unknown if ketamine improves cognitive symptoms. In rats, 2 weeks chronic intermittent cold (CIC) stress impairs reversal learning, a form of cognitive flexibility mediated by the orbitofrontal cortex (OFC) that we have used previously to model cognitive dysfunction in depression. We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-induced reversal learning deficit. Thus, in the present study we determined whether ketamine also corrects the stress-induced reversal learning deficit, and if JAK2/STAT3 signaling is involved in this effect. A single injection of ketamine (10 mg/kg, i.p.) 24 h prior to testing rescued the CIC stress-induced reversal learning deficit. CIC stress decreased JAK2 phosphorylation in the OFC, and ketamine restored pJAK2 levels within 2 h post injection. The JAK2 inhibitor AG490 given systemically or into the OFC at the time of ketamine injection prevented its beneficial effect on reversal learning. We then tested the role of JAK2/STAT3 in ketamine-induced plasticity in the OFC. Ketamine depressed local field potentials evoked in the OFC by excitatory thalamic afferent stimulation, and this was prevented by JAK2 inhibition in the OFC. Further, in both the OFC and primary cortical neurons in culture, ketamine increased expression of the neural plasticity-related protein Arc, and this was prevented by JAK2 inhibition. These results suggest that the JAK2/STAT3 signaling pathway is a novel mechanism by which ketamine exerts its therapeutic effects on stress-induced cognitive dysfunction in the OFC.
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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.