The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors.
Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2'-methoxy-phenyl)-1-[2'-(n-2''-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least in part, an interaction with 5-HT(1A/1B) and 5-HT(2C) receptors.
Wang
Rui
R
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, China.
Xu
Ying
Y
Wu
Hong-Li
HL
Li
Ying-Bo
YB
Li
Yu-Hua
YH
Guo
Jia-Bin
JB
Li
Xue-Jun
XJ
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism; D013550:Swimming
D000928:Antidepressive Agents; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D003474:Curcumin