ArticleInflammopharmacology2022
Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats.
Article in Inflammopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Brain-targeted intranasal aripiprazole via modified chitosan nanoparticles: controlled release, pharmacokinetics, and pharmacodynamics.Drug delivery and translational research · 2026Article
- Desloratadine Rescues Schizophrenia-like Phenotypes by Inhibiting the Pathogenic 5-HT2AR-PI3K/AKT/mTOR Signaling Axis.Molecular neurobiology · 2026Article
- Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis.Brain and behavior · 2026Article
- Esketamine ameliorates depression-like behavior in mice via modulation of the NRG1-ErbB4 pathway.Frontiers in psychiatry · 2026Article
- Unraveling Cannabidiol's Dual Modulatory Role in Schizophrenia: Network Pharmacology and In Vivo Validation of Neuroinflammatory and Behavioral Modulation.Molecular neurobiology · 2025Article
- Effects of Risperidone and Aripiprazole Antipsychotic Drugs on Behavioral Changes and the Expression Levels of DRD2, HTR2A, AKT1, and CACNA1C Genes in the Hippocampus of a Ketamine-induced Schizophrenia-like Rat Model.Journal of molecular neuroscience : MN · 2025Article
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis.European journal of medical research · 2025Article
- Review
- Epigallocatechin-3-gallate conjugated with selenium nanoparticles prevents neurological complications in rats exhibiting schizophrenia-like behaviors.Frontiers in pharmacology · 2025Article
- Five differentially expressed proteins identified to serve as potential blood biomarkers for schizophrenia screening based on proteomics.Frontiers in psychiatry · 2025Article
- Plasma microRNAs Associate Positive, Negative, and Cognitive Symptoms with Inflammation in Schizophrenia.International journal of molecular sciences · 2024Article
- The role and mechanism of NRG1/ErbB4 in inducing the differentiation of induced pluripotent stem cells into cardiomyocytes.BMC cardiovascular disorders · 2024Article
- Talin1 promotes HCC progression by regulating NRG1/PI3K/AKT pathway.Discover oncology · 2024Article
- nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus.Cell death & disease · 2024Article
- PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?The international journal of neuropsychopharmacology · 2024Review
- Proteomic insights into mental health status: plasma markers in young adults.Translational psychiatry · 2024Article
- Schizophrenia in the genetic era: a review from development history, clinical features and genomic research approaches to insights of susceptibility genes.Metabolic brain disease · 2024Review
- Study on correlations of BDNF, PI3K, AKT and CREB levels with depressive emotion and impulsive behaviors in drug-naïve patients with first-episode schizophrenia.BMC psychiatry · 2023Article
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3 authors at 1 institution in 1 country.
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Abstract
Schizophrenia is a common mental disorder affecting patients' thoughts, behavior, and cognition. Recently, the NRG1/ErbB4 signaling pathway emerged as a candidate therapeutic target for schizophrenia. This study investigates the effects of aripiprazole and sertindole on the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in ketamine-induced schizophrenia in rats. Young male Wistar rats received ketamine (30 mg/kg, intraperitoneally) for 5 consecutive days and aripiprazole (3 mg/kg, orally) or sertindole (2.5 mg/kg, orally) for 14 days. The proposed pathway was investigated by injecting LY294002 (a selective PI3K inhibitor) (25 μg/kg, intrahippocampal injection) 30 min before the drugs. Twenty-four hours after the last injection, animals were subjected to behavioral tests: the open field test, sucrose preference test, novel object recognition task, and social interaction test. Both aripiprazole and sertindole significantly ameliorated ketamine-induced schizophrenic-like behavior, as expected, because of their previously demonstrated antipsychotic activity. Besides, both drugs alleviated ketamine-induced oxidative stress and neurotransmitter level changes in the hippocampus. They also increased the gamma-aminobutyric acid and glutamate levels and glutamate decarboxylase 67 and parvalbumin mRNA expression in the hippocampus. Moreover, aripiprazole and sertindole increased the NRG1 and ErbB4 mRNA expression levels and PI3K, p-Akt, and mTOR protein expression levels. Interestingly, pre-injecting LY294002 abolished all the effects of the drugs. This study reveals that the antipsychotic effects of aripiprazole and sertindole are partly due to oxidative stress reduction as well as NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways activation. The NRG1/ErbB4 and PI3K signaling pathways may offer a new therapeutic approach for treating schizophrenia in humans.
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