ArticlePsychopharmacology2012
Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2017Pooled it
- Targeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene.Biological psychiatry · 2019Trial
- Kynurenine pathway dysregulation in attention-deficit hyperactivity disorder: Impact on N-methyl-D-aspartate receptors and phasic dopamine maturation.World journal of clinical pediatrics · 2026Review
- Targeting the SIRT6-TDO2/KYNA-mTOR axis rescues synaptic and cognitive deficits in fetal growth restriction offspring.Experimental & molecular medicine · 2026Article
- Fasting and Caloric Restriction Activate an ADIOL-NHR-91-Kynurenine Pathway Signaling Axis to Promote Healthspan.Aging cell · 2026Article
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Procognitive effects of methyl 2-amino-3-methoxybenzoate (or daopine) may involve the dorsal striatal anthranilic acid pathway and mutimetabolite-multitarget pharmacology.Behavioural pharmacology · 2025Article
- Parental kynurenine 3-monooxygenase genotype in mice directs sex-specific behavioral outcomes in offspring.Biology of sex differences · 2025Article
- Comparative analysis of Voxel-based morphometry using T1 and T2-weighted magnetic resonance imaging to explore the relationship between brain structure and cognitive abilities.Experimental brain research · 2025Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- The steroid hormone ADIOL promotes learning by reducing neural kynurenic acid levels.Genes & development · 2023Article
- Modulation of Kynurenic Acid Production by N-acetylcysteine Prevents Cognitive Impairment in Adulthood Induced by Lead Exposure during Lactation in Mice.Antioxidants (Basel, Switzerland) · 2023Article
- Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.Neurology international · 2023Review
- The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease.Nature reviews. Neurology · 2023Review
- Activated Tryptophan-Kynurenine metabolic system in the human brain is associated with learned fear.Frontiers in molecular neuroscience · 2023Article
- Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?Cellular and molecular life sciences : CMLS · 2022Review
- Cellular Localization of Kynurenine 3-Monooxygenase in the Brain: Challenging the Dogma.Antioxidants (Basel, Switzerland) · 2022Article
- Galantamine-Memantine Combination and Kynurenine Pathway Enzyme Inhibitors in the Treatment of Neuropsychiatric Disorders.Complex psychiatry · 2021Review
- Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleCognitive deficits represent a core symptom cluster in schizophrenia (SZ) that is predictive of outcome but not effectively treated by current antipsychotics. Thus, there is a need for validated animal models for testing potential pro-cognitive drugs.
objectiveAs kynurenic acid levels are increased in prefrontal cortex (PFC) of individuals with SZ, we acutely increased brain levels of this astrocyte-derived, negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs) by administration of its bioprecursor kynurenine and measured the effects on extracellular kynurenic acid and glutamate levels in PFC and also performance in a set-shifting task.
resultsInjections of kynurenine (100 mg/kg, i.p.) increased extracellular kynurenic acid (1,500%) and decreased glutamate levels (30%) in PFC. Kynurenine also produced selective deficits in set-shifting. Saline- and kynurenine-treated rats similarly acquired the compound discrimination and intra-dimensional shift (saline, 7.0 and 6.3 trials, respectively; kynurenine, 8.0 and 6.7). Both groups required more trials to acquire the initial reversal (saline, 15.3; kynurenine, 22.2). Only kynurenine-treated rats were impaired in acquiring the extra-dimensional shift (saline, 8.2; kynurenine, 21.3). These deficits were normalized by administering the α7nAChR positive allosteric modulator galantamine (3.0 mg/kg, i.p) prior to kynurenine, as trials were comparable between galantamine + kynurenine (7.8) and controls (8.2). Bilateral local perfusion of the PFC with galantamine (5.0 μM) also attenuated kynurenine-induced deficits.
conclusionsThese results validate the use of animals with elevated brain kynurenic acid levels in SZ research and support studies of drugs that normalize brain kynurenic acid levels and/or positively modulate α7nAChRs as pro-cognitive treatments for SZ.
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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.