PHARMACOLOGICAL MODELING OF SCHIZOPHRENIA: BEHAVIORAL ANALYSIS FOCUS ON THE AT1 RECEPTORS ROLE

OCCHIEPPO, VICTORIA BELÉN; JAIME, ANDREA; RODRIGUEZ, ANAHI; BASMADJIAN, OSVALDO MARTÍN; ARMONELLI, SAMANTA; BREGONZIO, CLAUDIA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Abstract/Resumen: Schizophrenia is a chronic mental illness with a high incidence worldwide affecting directly the patient?s life quality. This pathology is characterized by positive (hallucinations, delusions) and negative symptoms (social withdrawal), and cognitive deficit; that have been related to alterations in glutamatergic and dopaminergic neurotransmission. The administration of ketamine is a validated preclinical/animal model of schizophrenia in rodents, which reproduces the typical symptoms of this pathology. Brain Angiotensin II, through AT1 receptors (AT1-R), modulates dopaminergic and glutamatergic neurotransmission. Previously, we showed the AT1-R involvement in behavioral and neurochemical responses in an amphetamine model of schizophrenia. The present aim was to study AT1-R role in behavioral responses in a ketamine model of schizophrenia. Male Wistar rats (250-320 g) were administered with AT1-R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-6 or 1-10) and Ketamine (30 mg/kg i.p.), Acute: day 6 or subchronic: days 6-10. For Acute protocol (day 6), the locomotor activity, the social interaction and the novel object recognition were evaluated. For Subchronic protocol (after 14 days withdrawal) the same behavioral tests were evaluated at basal or challenge condition (Ketamine 15 mg/kg i.p.). Data were analyzed using two-way ANOVA, followed by Bonferroni test. Ketamine administration protocols resemble the described signs of schizophrenia since they induced augmented locomotor activity, social withdrawal and cognitive deficit. Interestingly, the AT1-R antagonist avoids the development and expression of these behavioral responses. Since the available therapeutic treatments for schizophrenia related disorders have low efficacy and high incidence of side-effects, new pharmacological approaches become necessary. However, further studies are needed to postulate the AT1-R as an alternative pharmacological target.