{"id":"CONICETDig_362da4d4fdc5d2b55a71894f57cac42f","dc:title":"Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor","dc:creator":"Bregonzio Diaz, Claudia","dc:date":"2024","dc: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\u201310) and ketamine\/saline (days 6\u201310). 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 ketamineinduced 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."],"dc:format":["application\/vnd.openxmlformats-officedocument.spreadsheetml.sheet"],"dc:language":["eng"],"dc:type":"dataset","dc:rights":["info:eu-repo\/semantics\/restrictedAccess","Datos sujetos al derecho de propiedad intelectual"],"dc:relation":["info:eu-repo\/grantAgreement\/Ministerio de Ciencia. Tecnolog\u00eda e Innovaci\u00f3n Productiva. Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica\/PICT 2016\/0403"],"dc:identifier":"https:\/\/repositoriosdigitales.mincyt.gob.ar\/vufind\/Record\/CONICETDig_362da4d4fdc5d2b55a71894f57cac42f"}