Folic acid administration prevents ouabain-induced hyperlocomotion and alterations in oxidative stress markers in the rat brain.
OBJECTIVE
Bipolar disorder (BD) is a chronic, prevalent, and highly debilitating psychiatric illness. Folic acid has been shown to have antidepressant-like effects in preclinical and clinical studies and has also been suggested to play a role in BD. The present work investigates the therapeutic value of folic acid supplementation in a preclinical animal model of mania induced by ouabain.


METHODS
Male Wistar rats were treated twice daily for seven days with folic acid (10, 50, and 100 mg/kg, p.o.) or the mood stabilizer lithium chloride (LiCl) (45 mg/kg, p.o.). One day after the last dose was given, the animals received an i.c.v. injection of ouabain (10 microM), a Na(+),K(+)-ATPase-inhibiting compound. Locomotor activity was assessed in the open-field test. Thiobarbituric acid-reactive substance (TBARS) levels, glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured in the cerebral cortex and hippocampus.


RESULTS
Ouabain (10 microM, i.c.v.) significantly increased motor activity in the open-field test, and seven days of pretreatment with folic acid (50 mg/kg, p.o.) or LiCl (45 mg/kg, p.o.) completely prevented this effect. Ouabain treatment elicited lipid peroxidation (increased TBARS levels) and reduced GPx activity in the hippocampus. GR activity was decreased in the cerebral cortex and hippocampus. These effects were prevented by pretreatment with folic acid and LiCl.


CONCLUSIONS
Our results show that folic acid, similarly to LiCl, produces a clear antimanic action and prevents the neurochemical alterations indicative of oxidative stress in an animal model of mania.
Brocardo
Patrícia S
PS
Department of Biochemistry, Centre of Biological Sciences, Federal University of Santa Catarina, Campus Universitario, Trindade, Florianopolis, Santa Catarina, Brazil.
Budni
Josiane
J
Pavesi
Eloísa
E
Franco
Jeferson L
JL
Uliano-Silva
Marcela
M
Trevisan
Rafael
R
Terenzi
Mariana G
MG
Dafre
Alcir L
AL
Rodrigues
Ana Lúcia S
AL
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005492:Folic Acid / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010042:Ouabain / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018692:Antimanic Agents; D015415:Biomarkers; D010042:Ouabain; D005492:Folic Acid; D018021:Lithium Chloride