It is well known that there is a complete local renineangiotensin system (RAS) in the central nervous system [1]. Angiotensin II (Ang II) is the main active peptide of the system, as the result of consecutive cleavage of angiotensinogen and angiotensin I

OCCHIEPPO, VICTORIA BELEN; BASMADJIAN, OSVALDO MARTIN; BAIARDI GUSTAVO; BREGONZIO, CLAUDIA

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

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. Ketamineadministration is a validated preclinical model that recreates thebehavioral and neurochemical features of the pathology, includingthe parvalbumin-expressing interneurons dysfunction. AngiotensinII, through AT1 receptors (AT1-R), modulates the dopaminergic andGABAergic neurotransmission. We evaluated the AT1-R role in thelong-term neuronal activation and behavioral alterations induced byrepeated ketamine administration. Adult male Wistar rats receivedAT1-R antagonist candesartan/vehicle (days 1-10) and ketamine/saline (days 6-10). After 14 days of drug-free, neuronal activationand behavioral analysis were performed. Locomotor activity, socialinteraction and novel object recognition tests were assessed atbasal conditions or after ketamine challenge. Immunostaining forc-Fos, GAD67 and parvalbumin were assessed after ketamine challengein cingulate, insular, piriform, perirhinal, and entorhinal cortices,striatum, and hippocampus. We found that ketamine-inducedlong-lasting schizophrenia-like behavioral alterations, and regional-dependent neuronal activation changes, involving the GABAergicneurotransmission system and the parvalbumin-expressing interneurons,were AT1-R-dependent. Our results add new evidence tothe wide spectrum of action of ketamine and strengthen the AT1-Rinvolvement in endurable alterations induced by psychostimulantsadministration, as well as their role in the development of psychiatricpathologies.