Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor

Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral a...

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Autores principales: Occhieppo, Victoria Belén, Basmadjian, Osvaldo Martín, Marchese, Natalia Andrea, Jaime, Andrea, Pérez, Mariela Fernanda, Baiardi, Gustavo Carlos, Bregonzio, Claudia
Formato: Artículo
Lenguaje:Español
Publicado: 2022
Materias:
QD Química
R Medicina (General)
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/3294/1/A_Occhieppo_Basmadjian_Marchese.pdf
Aporte de:
Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-3294
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spelling I38-R144-32942025-04-11T19:07:14Z http://pa.bibdigital.ucc.edu.ar/3294/ Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor Occhieppo, Victoria Belén Basmadjian, Osvaldo Martín Marchese, Natalia Andrea Jaime, Andrea Pérez, Mariela Fernanda Baiardi, Gustavo Carlos Bregonzio, Claudia QD Química R Medicina (General) Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT1 receptors (AT1-R), modulates the dopaminergic and GABAergic neurotransmission. We evaluated the AT1-R role in the long-term neuronal activation and behavioral alterations induced by repeated ketamine administration. Adult male Wistar rats received AT1-R antagonist candesartan/vehicle (days 1–10) and ketamine/saline (days 6–10). After 14 days of drug-free, neuronal activation and behavioral analysis were performed. Locomotor activity, social interaction and novel object recognition tests were assessed at basal conditions or after ketamine challenge. Immunostaining for c-Fos, GAD67 and parvalbumin were assessed after ketamine challenge in cingulate, insular, piriform, perirhinal, and entorhinal cortices, striatum, and hippocampus. Additionally, to evaluate the AT1-R involvement in acute ketamine psychotomimetic effects, the same behavioral tests were performed after 6 days of daily-candesartan and a single-ketamine administration. We found that ketamine-induced long-lasting schizophrenia-like behavioral alterations, and regional-dependent neuronal activation changes, involving the GABAergic neurotransmission system and the parvalbumin-expressing interneurons, were AT1-R-dependent. The AT1-R were not involved in the acute ketamine psychotomimetic effects. These results add new evidence to the wide spectrum of action of ketamine and strengthen the AT1-R involvement in endurable alterations induced by psychostimulants administration, previously proposed by our group, as well as their preponderant role in the development of psychiatric pathologies. 2022-05-03 info:eu-repo/semantics/article info:eu-repo/semantics/closedAccess application/pdf spa http://pa.bibdigital.ucc.edu.ar/3294/1/A_Occhieppo_Basmadjian_Marchese.pdf Occhieppo, Victoria Belén, Basmadjian, Osvaldo Martín, Marchese, Natalia Andrea, Jaime, Andrea, Pérez, Mariela Fernanda, Baiardi, Gustavo Carlos ORCID: https://orcid.org/0000-0003-4329-4398 <https://orcid.org/0000-0003-4329-4398> and Bregonzio, Claudia (2022) Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor. Behavioural Brain Research, 425. ISSN 0166-4328 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbr.2022.113809
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic QD Química
R Medicina (General)
spellingShingle QD Química
R Medicina (General)
Occhieppo, Victoria Belén
Basmadjian, Osvaldo Martín
Marchese, Natalia Andrea
Jaime, Andrea
Pérez, Mariela Fernanda
Baiardi, Gustavo Carlos
Bregonzio, Claudia
Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
topic_facet QD Química
R Medicina (General)
description Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT1 receptors (AT1-R), modulates the dopaminergic and GABAergic neurotransmission. We evaluated the AT1-R role in the long-term neuronal activation and behavioral alterations induced by repeated ketamine administration. Adult male Wistar rats received AT1-R antagonist candesartan/vehicle (days 1–10) and ketamine/saline (days 6–10). After 14 days of drug-free, neuronal activation and behavioral analysis were performed. Locomotor activity, social interaction and novel object recognition tests were assessed at basal conditions or after ketamine challenge. Immunostaining for c-Fos, GAD67 and parvalbumin were assessed after ketamine challenge in cingulate, insular, piriform, perirhinal, and entorhinal cortices, striatum, and hippocampus. Additionally, to evaluate the AT1-R involvement in acute ketamine psychotomimetic effects, the same behavioral tests were performed after 6 days of daily-candesartan and a single-ketamine administration. We found that ketamine-induced long-lasting schizophrenia-like behavioral alterations, and regional-dependent neuronal activation changes, involving the GABAergic neurotransmission system and the parvalbumin-expressing interneurons, were AT1-R-dependent. The AT1-R were not involved in the acute ketamine psychotomimetic effects. These results add new evidence to the wide spectrum of action of ketamine and strengthen the AT1-R involvement in endurable alterations induced by psychostimulants administration, previously proposed by our group, as well as their preponderant role in the development of psychiatric pathologies.
format Artículo
author Occhieppo, Victoria Belén
Basmadjian, Osvaldo Martín
Marchese, Natalia Andrea
Jaime, Andrea
Pérez, Mariela Fernanda
Baiardi, Gustavo Carlos
Bregonzio, Claudia
author_facet Occhieppo, Victoria Belén
Basmadjian, Osvaldo Martín
Marchese, Natalia Andrea
Jaime, Andrea
Pérez, Mariela Fernanda
Baiardi, Gustavo Carlos
Bregonzio, Claudia
author_sort Occhieppo, Victoria Belén
title Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
title_short Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
title_full Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
title_fullStr Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
title_full_unstemmed Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor
title_sort schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve angiotensin ii at1 receptor
publishDate 2022
url http://pa.bibdigital.ucc.edu.ar/3294/1/A_Occhieppo_Basmadjian_Marchese.pdf
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