Efficacy of folic acid as an adjunct to lithium therapy on manic-like behaviors, oxidative stress and inflammatory parameters in an animal model of mania

• Published in: Metabolic brain disease 2020-02, Vol.35 (2), p.413-425
• Main Authors: Menegas, Samira, Dal-Pont, Gustavo C., Cararo, José H., Varela, Roger B., Aguiar-Geraldo, Jorge M., Possamai-Della, Taise, Andersen, Monica L., Quevedo, João, Valvassori, Samira S.
• Format: Article
• Language: English
• Subjects: Affective disorders; Amphetamine - toxicity; Amphetamines; Animal models; Animals; Antimanic Agents - administration & dosage; Biochemistry; Biomedical and Life Sciences; Biomedicine; Central Nervous System Stimulants - toxicity; Cortex (frontal); Damage; Disease Models, Animal; Drug abuse; Drug Therapy, Combination; Exploratory behavior; Field tests; Folic acid; Folic Acid - administration & dosage; Glutathione; Glutathione peroxidase; Glutathione reductase; IL-1β; Inflammation; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Lipids; Lithium; Lithium - administration & dosage; Male; Mania - chemically induced; Mania - drug therapy; Mania - metabolism; Mathematical models; Metabolic Diseases; Neostriatum; Neurology; Neurosciences; Oncology; Open-field behavior; Original Article; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Parameters; Peroxidase; Rats; Rats, Wistar; Reductases; Risk taking; Rodents; Sodium chloride; Stereotyped behavior; Therapy; Treatment Outcome; Tumor necrosis factor-α; Vitamin E; Water treatment
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-019-00503-3

Evaluate the efficacy of folic acid (FA) as a therapeutic adjunct to lithium (Li) on the manic-like behaviors as well as parameters of oxidative stress and inflammation in an animal model of mania induced by m-amphetamine (m-AMPH). Wistar rats first received m-AMPH or saline (NaCl 0.9%, Sal) for 14 days. Between the 8th and 14th day, rats were treated with water, Li, FA or a combination of thereof drugs (Li + FA). Manic-like behaviors were assessed in the open-field test. Oxidative stress and inflammation parameters were assessed in the frontal cortex, striatum, and hippocampus. Administration of m-AMPH in rats significantly enhanced the exploratory and locomotor behaviors, as well as the risk-taking and stereotypic behaviors. Li + FA reversed these behavioral alterations elicited by m-AMPH. Administration of this psychostimulant also increased oxidative damage to lipids and proteins, whereas Li + FA reversed these oxidative damages. m-AMPH also induced an increase in the glutathione peroxidase (GPx) activity and a decrease in the glutathione reductase (GR) activity. Li + FA reversed the alteration in GR activity, but not in GPx activity. In addition, m-AMPH increased the IL-1β and TNF-α levels in the rat brain; Li + FA combined therapy reversed the alterations on these inflammatory parameters. FA administration per se reduced the increased TNF-α content induced by m-AMPH. Present study provides evidence that FA is effective as an adjunct to Li standard therapy on manic-like behaviors, oxidative stress and inflammatory parameters in a model of mania induced by m-AMPH.