Behavioral and pharmacological challenges unmask ketamine long-term alterations: AT1 receptors role

RODRIGUEZ, A.; JAIME, A.; OCCHIEPPO. V.B.; MARCHESE, N.A.; BREGONZIO, C.

Carlos Paz

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de Investigación en Neurociencias

Ketamine administration, a validated animal model of schizophrenia, resemblessome of the behavioral symptoms and structural alterations of the pathology. Ourgroup has evidences supporting Angiotensin II AT1 receptors (AT1-R) role inbehavioral, neuroinflammatory and neurochemical responses in amphetamine andketamine models of schizophrenia. The present work aims to study astrogliosisand neuronal survival in somatosensory cortex (S1) in ketamine treated animalsand the AT1-R involvement. In addition, hot plate test was used as behavioraloutput of S1. Methods: Male Wistar rats (250-320g) were administered with AT1-Rantagonist Candesartan/vehicle (3mg/kg p.o., day1-6) and Ketamine/saline(30mg/kg i.p., day 6-10). Hot plate test was performed under naive conditions (day0) and after 14 days of withdrawal of ketamine treatment. On day 25, glial reactivity(GFAP) and neuronal survival (cresyl violet) were evaluated at basal condition andafter ketamine challenge (15mg/kg i.p.; -24hs). Data were analyzed by factorialANOVA. Results: Ketamine treated animals displayed an increased thermalnociception. Ketamine challenge increased neuronal death, without astrogliosis,that was prevented by AT1-R blockade. At basal conditions, no changes wereobserved. Conclusion: ketamine-induced alterations were prevented by AT1-Rblockade, supporting the protective effects of AT1-R blockers described for severalbrain diseases.