ArticlePsychopharmacology2014
Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats.
Article in Psychopharmacology, 2014. 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, 68 citations in OpenAlex.
- Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: a randomized, double-blind, placebo-controlled trial.The international journal of neuropsychopharmacology · 2024Trial
- Review
- Arginine Metabolism and Adenosine Receptor Signals in the Cerebellum Contribute to Nicotine Withdrawal-Induced Anxiety/Depression-Like Behaviours.Addiction biology · 2025Article
- Impact of istradefylline on motor and non-motor symptoms in patients with Parkinson's disease: Subanalysis of the ISTRA ADJUST PD.Clinical parkinsonism & related disorders · 2025Article
- Brain Specific RagA Overexpression Triggers Depressive-Like Behaviors in Mice via Activating ADORA2A Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats.Molecular neurobiology · 2023Article
- Lateral septum adenosine ANature communications · 2023Article
- The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks.Frontiers in cellular neuroscience · 2023Review
- [Adenosine A2A Receptor Antagonists as a Treatment Option for Parkinson's Disease?]Fortschritte der Neurologie-Psychiatrie · 2022Article
- A Pattern to Link Adenosine Signaling, Circadian System, and Potential Final Common Pathway in the Pathogenesis of Major Depressive Disorder.Molecular neurobiology · 2022Review
- The Role of the Adenosine System on Emotional and Cognitive Disturbances Induced by Ethanol Binge Drinking in the Immature Brain and the Beneficial Effects of Caffeine.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.Molecular diversity · 2022Review
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist.Molecules (Basel, Switzerland) · 2022Article
- Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets.International journal of molecular sciences · 2022Review
- Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives with High Affinity for Both the Adenosine APharmaceuticals (Basel, Switzerland) · 2021Article
- Discovery of novel dual adenosine A1/A2A receptor antagonists using deep learning, pharmacophore modeling and molecular docking.PLoS computational biology · 2021Article
- Novel curcumin analog (cis-trans curcumin) as ligand to adenosine receptors APharmacological research · 2021Article
- Purinergic Signaling and Related Biomarkers in Depression.Brain sciences · 2020Article
- Striatopallidal neurons control avoidance behavior in exploratory tasks.Molecular psychiatry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleIstradefylline, an adenosine A2A receptor antagonist, improves motor function in animal models of Parkinson's disease (PD) and in patients with PD. In addition, some A2A antagonists exert antidepressant-like activity in rodent models of depression, such as the forced swim and the tail suspension tests.
objectiveWe have investigated the effect of istradefylline on depression-like behaviors using the rat learned helplessness (LH) model.
resultsAcute, as well as chronic, oral administration of istradefylline significantly improved the inescapable shock (IES)-induced escape deficit with a degree of efficacy comparable to chronic treatment with the tricyclic antidepressant desipramine and the selective serotonin (5-HT) reuptake inhibitor, fluoxetine. Both the A1/A2A receptor nonspecific antagonist theophylline and the moderately selective antagonist CGS15943, but not the A1 selective antagonist DPCPX, ameliorated the IES-induced escape deficit. The enhancement of escape response by istradefylline was reversed by a local injection of the A2A specific agonist CGS21680 either into the nucleus accumbens, the caudate-putamen, or the paraventricular nucleus of the hypothalamus, but not by the A1 specific agonist R-PIA into the nucleus accumbens. Moreover, neither the 5-HT2A/2C receptor antagonist methysergide or the adrenergic α 2 antagonist yohimbine, nor the β-adrenergic antagonist propranolol, affected the improvement of escape response induced by istradefylline.
conclusionsIstradefylline exerts antidepressant-like effects via modulation of A2A receptor activity which is independent of monoaminergic transmission in the brain. Istradefylline may represent a novel treatment option for depression in PD as well as for the motor symptoms.
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.