Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: evidence for the involvement of monoaminergic systems.
The relationship between depression and monoaminergic systems has been hypothesized for many years. In this study, we have investigated the possible antidepressant-like effect of scopoletin, a coumarin from Polygala sabulosa in the tail suspension test and forced swimming test. Moreover, the ability of scopoletin to reverse the depression-like behavior in the forced swimming test induced by immobility stress in mice was evaluated. Scopoletin reduced the immobility time in the tail suspension test (10-100mg/kg, p.o.), but not in the forced swimming test. Fluoxetine (positive control) decreased the immobility time in the forced swimming and tail suspension tests (20mg/kg, p.o. and 10mg/kg. p.o., respectively). Immobility stress caused an increase in the immobility time in the forced swimming test (depression-like behavior), which was reversed by scopoletin (1-100mg/kg, p.o.) and fluoxetine (10mg/kg, p.o.). Scopoletin produced no psychostimulant effect in the open-field test. The pretreatment of mice with ketanserin (5mg/kg, i.p., a preferential 5-HT(2A) receptor antagonist), prazosin (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), haloperidol (0.2mg/kg, i.p., a dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist), but not WAY100635 (0.1mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) prevented the antidepressant-like effect of scopoletin (10mg/kg, p.o.) in the tail suspension test. The results indicate that its antidepressant-like effect is dependent on the serotonergic (5-HT(2A) receptors), noradrenergic (alpha(1)- and alpha(2)-adrenoceptors) and dopaminergic (dopamine D(1) and D(2) receptors) systems.
Capra
Juliano C
JC
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.
Cunha
Mauricio P
MP
Machado
Daniele G
DG
Zomkowski
Andrea D E
AD
Mendes
Beatriz G
BG
Santos
Adair Roberto S
AR
Pizzolatti
Moacir G
MG
Rodrigues
Ana Lúcia S
AL
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003374:Coumarins / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D019417:Hindlimb Suspension; D051379:Mice; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D031801:Polygala / Q000737:chemistry*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D011897:Random Allocation; D017982:Receptors, Biogenic Amine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012603:Scopoletin / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D003374:Coumarins; D018377:Neurotransmitter Agents; D010936:Plant Extracts; D020033:Protein Isoforms; D017982:Receptors, Biogenic Amine; D012603:Scopoletin