Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine

Abstract Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an anim...

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Published in:	Journal of psychiatric research Vol. 81; pp. 23 - 35
Main Authors:	Zugno, Alexandra I, Canever, Lara, Heylmann, Alexandra S, Wessler, Patrícia G, Steckert, Amanda, Mastella, Gustavo A, de Oliveira, Mariana B, Damázio, Louyse S, Pacheco, Felipe D, Calixto, Octacílio P, Pereira, Flávio P, Macan, Tamires P, Pedro, Thayara H, Schuck, Patrícia F, Quevedo, João, Budni, Josiane
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-10-2016
Subjects:	Animals Attention Deficit and Disruptive Behavior Disorders - drug therapy Attention Deficit and Disruptive Behavior Disorders - etiology Behavioral Disease Models, Animal Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists - toxicity Folic acid Folic Acid - therapeutic use Interpersonal Relations Ketamine Ketamine - toxicity Lipid Metabolism - drug effects Locomotion - drug effects Male Malondialdehyde - metabolism Oxidative stress Oxidative Stress - drug effects Protein Carbonylation - drug effects Psychiatry Rats Rats, Wistar Schizophrenia Schizophrenia - chemically induced Schizophrenia - complications Superoxide Dismutase - metabolism Time Factors Vitamin B Complex - therapeutic use Behavioral Schizophrenia Oxidative stress Ketamine Folic acid
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Summary:	Abstract Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal's locomotion. This study showed that the administration of folic acid over 7 days was unable to prevent hyper locomotion. In contrast, folic acid (10 and 50 mg/kg) administrated over a period of 14 days, was able to partially prevent the hyper locomotion. Our data indicates that both acute and chronic administrations of ketamine increased the time to first contact between the animals, while the increased latency for social contact was completely prevented by folic acid (5, 10 and 50 mg/kg). Chronic and acute administrations of ketamine also increased lipid peroxidation and protein carbonylation in brain. Folic acid (10 and 50 mg/kg) supplements showed protective effects on the oxidative damage found in the different brain structures evaluated. All together, the results indicate that nutritional supplementation with folic acid provides promising results in an animal model of schizophrenia induced by ketamine.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3956 1879-1379
DOI:	10.1016/j.jpsychires.2016.06.013