Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life

• DOI: 10.1016/j.neuroscience.2017.04.016
• Publication Date: 2017-04-20T05:02:06Z
• Authors: Gislaine Z. Réus; Lutiana R. Simões; Gabriela D. Colpo; Giselli Scaini; Jean P. Oses; Jaqueline S. Gene...; Alan R. Prossin; Rima Kaddurah-Daouk; João Quevedo; Tatiana Barichello
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Behavior, Animal; Brain; Prefrontal Cortex; Hippocampus; Corpus Striatum; 3. Good health; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; Animals, Newborn; Schizophrenia; Animals; Cytokines; Encephalitis; Female; Ketamine; Rats, Wistar; Locomotion

Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, levels of cytokines, and the locomotor activity of IA in a schizophrenia animal model in which neonatal male Wistar rats were administered with an injection of LPS (50μg/kg) on postnatal day 3 and different doses of ketamine (5, 15 and 25mg/kg) for 7days during adulthood. Rats LPS-induced did not have locomotor activity alterations. Locomotor activity was elevated in neonatally saline-injected in the higher dose ketamine-treated animals. Carbonyl protein in the prefrontal cortex (PFC), hippocampus and striatum were increased in the LPS- and saline-induced in the ketamine (25mg/kg)-treated animals. Lipid damage occurred in the PFC, striatum and hippocampus in the LPS- and saline-induced in the ketamine (15 and 25mg/kg) -treated animals. In the hippocampus the superoxide dismutase (SOD) was decreased in the LPS- and saline-induced in the ketamine-treated with the dose of 25mg/kg. In the PFC SOD was reduced in the LPS-induced in the ketamine (25mg/kg)-treated animals. Catalase in the PFC and hippocampus was reduced in the LPS- and saline-induced in the ketamine (25mg/kg)-treated animals. Pro- and anti-inflammatory cytokines were lower in the brains of LPS-induced in the higher dose ketamine-treated rats. IA influences the locomotor activity and cytokine levels induced by ketamine, and it has a negative effect in potentiating the oxidative stress by higher doses of ketamine in the brain.