EVALUATION OF PUBERTAL TREATMENT WITH THE ANTIOXIDANT N-ACETYL-CYSTEINE ON BEHAVIOR AND CYTOKINES IN MAM RAT MODEL OF IMPAIRed NEURODEVELOPMENT
To understand the pathophysiology of schizophrenia, studies have found changes in dopaminergic and glutamatergic neurotransmissions, as well as a reduction in inhibitory interneurons that express parvalbumin (PVI) in the prefrontal cortex (PFC) and ventral hippocampus. This process is related to oxidative stress and increased neuroinflammation. The antioxidant N-acetyl-L-cysteine (NAC) reduced physiological and behavioral changes in several animal models of schizophrenia, but its effect during the pubertal phase has been little studied. The animal model of schizophrenia based on neurodevelopmental impairment through the administration of methylazoxymethanol acetate (MAM) in rats on the 17th gestational day (GD17) induces behavioral, neuronal and physiological changes consistent with those in humans. Treatment of MAM model animals with NAC has shown promising results, however, studies on its anti-inflammatory properties are scarce. This work aims to evaluate behavioral changes in male rats of MAM model, under acute or chronic treatment with NAC in the pubertal phase, investigating pro- and anti-inflammatory cytokine blood levels, correlated with behavioral responses in. On GD17, pregnant rats were treated with 25 mg/kg/ml) MAM or saline. At 45 days of age, i.p. treatment was started with saline or NAC 250 mg/ kg. One hour after the first application, the Acute Assessment was carried out, including pre-pulse inhibition tests (PPI), social interaction (SI) and locomotion in the arena. These animals were treated chronically for 15 days. Twenty-four hours after the last dose, the Chronic Assessment was performed, with the same tests. MAM rats showed an increase in the total distance traveled in the arena, a decrease in active interaction time and greater time in self-grooming behavior in the IS, compared to the saline group. Treatment with NAC reversed the increase in self-grooming duration, rearing and prevented IS deficit. There was no significant effect of the treatments on the levels of cytokines in the blood, however the levels of IL-10 and IL-1ß positively correlated with SI. These data indicate that treatment with NAC in the pubertal phase has mainly effects in behaviors related to anxiety. Further studies are needed to investigate the effects of those treatments in adulthood.