Bipolar disorder (BD) is a common and severe
mood disorder associated with higher rates of suicide and disability.
Ouabain, a
Na(+)/K(+)-ATPase inhibitor, induces behavioral changes in rats and has been used as a model of
mania. The aim of this study was to investigate if
diphenyl diselenide [(PhSe)(2)], an organoselenium compound with pharmacological properties, is effective against
ouabain-induced hyperactivity and alterations in cerebral oxidative status of rats. Male Wistar rats were treated with a single dose of (PhSe)(2) (50 mg/kg, p.o.) 30 min before i.c.v. injection of
ouabain (5 μl, 10(-5) M) or with the mood stabilizer,
lithium chloride (LiCl) (45 mg/kg, p.o.), twice a day, for 7 days before the administration of
ouabain. Open-field locomotion was quantified after
ouabain administration.
Thiobarbituric acid reactive substances (
TBARS), oxidatively modified
proteins,
tyrosine nitration,
ascorbic acid and non-
protein thiols (NPSH) levels and
superoxide dismutase (SOD),
catalase (CAT),
glutathione peroxidase (GPx) and
glutathione reductase (GR) activities were determined in the whole brain.
Ouabain increased locomotor activity in the open-field test and pretreatment with (PhSe)(2) or LiCl blocked this effect. In addition,
ouabain increased lipid peroxidation and oxidatively modified
proteins, demonstrated by a significant increase in
TBARS levels and carbonyl content, which were attenuated by pretreatment with (PhSe)(2) or LiCl. The activities of SOD and CAT were increased by
ouabain. LiCl was effective on preventing the increases of both
enzyme activities, but (PhSe)(2) attenuated the
ouabain effect in SOD activity. GPx and GR activities,
ascorbic acid, NPSH and
tyrosine nitration levels were not altered in all experimental groups. Similarly to LiCl, (PhSe)(2) produced an antimanic-like action, since it was effective against the locomotor hyperactivity elicited by
ouabain. The results also indicated that (PhSe)(2) was effective against oxidative stress caused by
ouabain in rats.