ArticleJournal of molecular neuroscience : MN2013
α-Lipoic acid interaction with dopamine D2 receptor-dependent activation of the Akt/GSK-3β signaling pathway induced by antipsychotics: potential relevance for the treatment of schizophrenia.
Article in Journal of molecular neuroscience : MN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review.Metabolic brain disease · 2019Pooled it
- Effect of add-on alpha lipoic acid on psychopathology in patients with treatment-resistant schizophrenia: a pilot randomized double-blind placebo-controlled trial.Psychopharmacology · 2022Trial
- Exploring the Role of Alpha Lipoic Acid in the Treatment of Traumatic Brain Injury: Pathways and Perspectives.Neurocritical care · 2026Review
- Alpha-lipoic acid administration affects psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease.Journal of diabetes and metabolic disorders · 2022Article
- Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine.Neurochemical research · 2021Article
- Haloperidol elicits oxidative damage in the brain of rats submitted to the ketamine-induced model of schizophrenia.Brain research bulletin · 2021Article
- Review
- Residues and residue pairs of evolutionary importance differentially direct signaling bias of D2 dopamine receptors.The Journal of biological chemistry · 2019Article
- Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review.Current neuropharmacology · 2017Review
- Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Dopamine D2 receptors' effects on renal inflammation are mediated by regulation of PP2A function.American journal of physiology. Renal physiology · 2016Article
- The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress.Oxidative medicine and cellular longevity · 2016Review
- Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats.Molecular brain · 2015Article
- Implication of the ERK/MAPK pathway in antipsychotics-induced dopamine D2 receptor upregulation and in the preventive effects of (±)-α-lipoic acid in SH-SY5Y neuroblastoma cells.Journal of molecular neuroscience : MN · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic administration of antipsychotics has been associated with dopamine D2 receptor (D2R) upregulation and tardive dyskinesia. We have previously shown that haloperidol, a first-generation antipsychotic (FGA), exerted an increase in D2R expression and oxidative stress and that (±)-α-lipoic acid reversed its effect. Previous studies have implicated the Akt/glycogen synthase kinase-3β (GSK-3β) signaling pathway in antipsychotic action. These findings led us to examine whether the Akt/GSK-3β pathway was involved in D2R upregulation and oxidative stress elicited by antipsychotics and, in (±)-α-lipoic acid-induced reversal of these phenomena, in SH-SY5Y cells. Antipsychotics increased phosphorylation of Akt and GSK-3β, and additive effects were observed with (±)-α-lipoic acid. GSK-3β inhibitors reversed haloperidol-induced overexpression of D2R mRNA levels but did not affect haloperidol-induced oxidative stress. Sustained antipsychotic treatment increased β-arrestin-2 and D2R receptor interaction. Regarding Akt/GSK-3β downstream targets, antipsychotics increased β-catenin levels, whereas (±)-α-lipoic acid induced an elevation of mTOR activation. These results suggest (1) that the effect of antipsychotics on the Akt/GSK-3β pathway in SH-SY5Y cells is reminiscent of their in vivo action, (2) that (±)-α-lipoic acid partially synergizes with antipsychotic drugs (APDs) on the same pathway, and (3) that the Akt/GSK-3β signaling cascade is not involved in the preventive effect of (±)-α-lipoic acid on antipsychotics-induced D2R upregulation.
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Registered trials
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