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

OCCHIEPPO VICTORIA B; BASMADJIAN OSVALDO M; MARCHESE NATALIA A.; BREGONZIO CLAUDIA

Berlin

Congreso; XI FENS Forum 2018; 2018

Federation European of Neuroscience (FENS)

Schizophrenia is a chronic mental illness that directly affects the patient?s life quality, due to a large number of distressing symptoms 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. Considering the low efficacy and high incidence of side-effects of the available therapeutic treatments new pharmacological approaches become necessary. Based on the evidences supporting a key role of Angiotensin II AT1 receptors (AT1-R) in dopaminergic and glutamatergic neurotransmission and on our previous findings from an amphetamine model of schizophrenia; the present work was focus on the study of AT1-R involvement in behavioral and glial responses in a ketamine model of schizophrenia. For this purpose male Wistar rats (250-320g) were administered with AT1-R-blocker 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 in prefrontal cortex and ventral tegmental area, were evaluated. Data were analyzed with two-way-ANOVA followed by Bonferroni test. In our model, we observed increased basal glial reactivity, sensitized locomotor activity and cognitive deficit after ketamine challenge; resembling characteristic outputs of the pathology. Remarkably, we showed the AT1-R involvement in the development of these behavioral and structural alterations. We conclude that our results are promising in the search of new pharmacological tools, like AT1-R-blockers as schizophrenia palliative