Interaction of clozapine with metformin in a schizophrenia rat model

Abstract The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of...

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Autores principales:	G. Horvath, G. Kis, G. Kekesi, A. Büki, L. G. Adlan, E. Szűcs, H. El Heni, S. Benyhe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d9dba62c9c244dd8d679eb05da2ea09
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spelling	oai:doaj.org-article:2d9dba62c9c244dd8d679eb05da2ea092021-12-02T16:45:41ZInteraction of clozapine with metformin in a schizophrenia rat model10.1038/s41598-021-96478-22045-2322https://doaj.org/article/2d9dba62c9c244dd8d679eb05da2ea092021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96478-2https://doaj.org/toc/2045-2322Abstract The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.G. HorvathG. KisG. KekesiA. BükiL. G. AdlanE. SzűcsH. El HeniS. BenyheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q G. Horvath G. Kis G. Kekesi A. Büki L. G. Adlan E. Szűcs H. El Heni S. Benyhe Interaction of clozapine with metformin in a schizophrenia rat model
description	Abstract The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.
format	article
author	G. Horvath G. Kis G. Kekesi A. Büki L. G. Adlan E. Szűcs H. El Heni S. Benyhe
author_facet	G. Horvath G. Kis G. Kekesi A. Büki L. G. Adlan E. Szűcs H. El Heni S. Benyhe
author_sort	G. Horvath
title	Interaction of clozapine with metformin in a schizophrenia rat model
title_short	Interaction of clozapine with metformin in a schizophrenia rat model
title_full	Interaction of clozapine with metformin in a schizophrenia rat model
title_fullStr	Interaction of clozapine with metformin in a schizophrenia rat model
title_full_unstemmed	Interaction of clozapine with metformin in a schizophrenia rat model
title_sort	interaction of clozapine with metformin in a schizophrenia rat model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d9dba62c9c244dd8d679eb05da2ea09
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Interaction of clozapine with metformin in a schizophrenia rat model

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