Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system.
Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] is a seleno-organic compound which possesses a potent antioxidant activity and has been shown to exert neuroprotective effects in vitro and in vivo in a variety of pro-oxidative insults. The present study investigates a possible antidepressant activity of ebselen using two predictive tests for antidepressant activity in rodents: the forced swimming test and tail suspension test. Additionally, the mechanisms involved in the antidepressant-like effect of ebselen in mice were also assessed. Ebselen (10 mg/kg, s.c.) decreased the immobility time in the forced swimming test without accompanying changes in ambulation in the open-field test. In contrast, the administration of ebselen (10-30 mg/kg) did not produce any effect in the tail suspension test. The anti-immobility effect of ebselen (10 mg/kg, s.c.) was not prevented by pre-treatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a serotonin 5-HT(1A) receptor antagonist) or ketanserin (5 mg/kg, i.p., a serotonin 5-HT(2A/2C) receptor antagonist). On the other hand, the pre-treatment of mice with prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist) completely blocked the antidepressant-like effect of ebselen (10 mg/kg, s.c.) in the forced swimming test. It may be concluded that ebselen produces an antidepressant-like effect in the forced swimming test that seems to be dependent on its interaction with the noradrenergic and dopaminergic systems, but not with the serotonergic system.
Posser
Thaís
T
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil.
Kaster
Manuella P
MP
Baraúna
Sara Cristiane
SC
Rocha
João B T
JB
Rodrigues
Ana Lúcia S
AL
Leal
Rodrigo B
RB
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D054833:Isoindoles; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D001393:Azoles; D015306:Biogenic Monoamines; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D013469:Sulpiride