Cariprazine Exhibits Anxiolytic and Dopamine D3 Receptor-Dependent Antidepressant Effects in the Chronic Stress Model

The International Journal of Neuropsychopharmacology
Vanja DuricRonald S Duman

Abstract

Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the United States for the treatment of schizophrenia and bipolar mania. We recently demonstrated that cariprazine also has significant antianhedonic-like effects in rats subjected to chronic stress; however, the exact mechanism of action for cariprazine's antidepressant-like properties is not known. Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors. Wild-type and D3-knockout mice were exposed to chronic unpredictable stress for up to 26 days, treated daily with vehicle, imipramine (20 mg/kg), aripiprazole (1 and 5 mg/kg), or cariprazine (0.03, 0.1, 0.2, and 0.4 mg/kg), and tested in behavioral assays measuring anhedonia and anxiety-like behaviors. Results showed that cariprazine significantly attenuated chronic unpredictable stress-induced anhedonic-like behavior in wild-type mice, demonstrating potent antidepressant-like effects comparable with aripiprazole and the tricyclic antidepressant imipramine. This antianhedonic-like effect of cariprazine was not observed in D3-knockout mice, suggesting that the cariprazine antidepressant-like activity is mediated ...Continue Reading

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Citations

May 4, 2018·Expert Opinion on Drug Discovery·Anna WesołowskaMarcin Kołaczkowski
Feb 1, 2019·Journal of Psychosocial Nursing and Mental Health Services·Barbara J Limandri
Feb 13, 2019·Expert Review of Neurotherapeutics·Renee-Marie Ragguett, Roger S McIntyre
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Jan 8, 2021·Journal of Psychopharmacology·Gabriella NyitraiAndrás Czurkó
Jan 31, 2021·Behavioural Brain Research·Daria A ChestnykhChristian P Müller
Aug 9, 2021·Molecular Neurobiology·Matej ĽuptákJana Hroudová

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