Involvement of monoaminergic systems in the antidepressant-like effect of nobiletin.
Nobiletin isolated from citrus peels up-regulates synaptic transmission and improves memory impairment in rodents. This study investigated the antidepressant-like effect of nobiletin in the forced swimming test (FST) and tail suspension test (TST) in mice. Additionally, the monoaminergic mechanisms involved in the antidepressant-like effect of nobiletin in mice were also assessed. Nobiletin (25, 50 and 100mg/kg, p.o.) decreased the immobility time in both the FST and TST without locomotor alterations in the open-field test (OFT). The anti-immobility effect of nobiletin (50mg/kg, p.o.) was completely prevented by the pretreatment of mice with WAY 100635 (0.1mg/kg, s.c., a serotonin 5-HT(1A) receptor antagonist), cyproheptadine (3mg/kg, i.p., a serotonin 5-HT(2) receptor antagonist), prazosin (62.5μg/kg, i.p., an α(1)-adrenoceptor antagonist), SCH23390 (0.05mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist). On the other hand, the pretreatment of mice with yohimbine (1mg/kg, i.p., an α(2)-adrenoceptor antagonist) or propranolol (5mg/kg, i.p., a β-adrenoceptor antagonist) did not block the antidepressant-like effect of nobiletin in the TST. Taken together, the data demonstrated that nobiletin produced an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. Thus, the present study suggests the therapeutic potential of this dietary flavonoid for the treatment of depression.
Institute of Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China. litaoyi@hqu.edu.cn
Li-Tao
LT
Yi
He-Li
HL
Xu
Jing
J
Feng
Xia
X
Zhan
Li-Pan
LP
Zhou
Cun-Cang
CC
Cui
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001552:Benzazepines / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D047309:Flavones / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005473:Fluoxetine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019417:Hindlimb Suspension / Q000523:psychology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D015016:Yohimbine / Q000494:pharmacology
D018674:Adrenergic Antagonists; D000928:Antidepressive Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D047309:Flavones; D010879:Piperazines; D011725:Pyridines; C534628:SCH 23390; D012702:Serotonin Antagonists; D005473:Fluoxetine; D015016:Yohimbine; D003533:Cyproheptadine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D013469:Sulpiride; D011433:Propranolol; C008661:nobiletin; D011224:Prazosin