Angiotensin II AT1 receptors are involved in behavioral and glial responses in a ketamine model of schizophrenia

OCCHIEPPO, VICTORIA BELÉN; BASMADJIAN, O.M.; MARCHESE, N.A.; PEREZ. M.F.; BREGONZIO, C.

Congreso; 11th FENS FORUM; 2018

Federation of European Neuroscience Societies

Schizophrenia is a chronic mental illness that directly affects the patient?s life quality, due to a large number of distressing symptoms such as cognitive deficit, positive and negative symptoms. These behavioral anomalies have been related to alterations in glutamatergic and dopaminergic neurotransmission, concomitant with altered glial structure. Ketamine administration has been validated as a preclinical animal model of schizophrenia which resembles behavioral symptoms, as well as some brain structural alterations. Since the available therapeutic treatments for this illness have low efficacy and high incidence of side-effects, new pharmacological approaches become necessary. Brain Angiotensin II, through AT1 receptors (AT1-R), modulates dopaminergic and glutamatergic neurotransmission. Previously, we found evidences showing AT1-R involvement in behavioral and neurochemical responses in an amphetamine model of schizophrenia. The aim for the present work was to study AT1-R involvement in behavioral and glial responses in an animal model of schizophrenia induced by ketamine. Male Wistar rats (250-320g) were administered with AT1-R antagonist Candesartan/vehicle (3mg/kg p.o., day 1-6) and Ketamine (30mg/kg i.p., day 6-10). On day 24, the locomotor activity, novel object recognition and glial reactivity, were evaluated. Data were analyzed with two-way ANOVA, and repeated measures two-way ANOVA for locomotor activity, followed by Bonferroni test. We observed augmented locomotor activity, cognitive deficit and increased glial reactivity after Ketamine exposure. Interestingly, the AT1-R antagonist blunted these behavioral and structural alterations, supporting the protective effects of AT1-R-blockers described for several brain diseases. However, further evidences are necessary to point to AT1-R as a pharmacological target in schizophrenia.