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; BREGONZIO, CLAUDIA

BEHAVIOURAL BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2022 vol. 425

0166-4328

chizophrenia 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. Immunosta