Antidepressant-like effects of curcumin on serotonergic receptor-coupled AC-cAMP pathway in chronic unpredictable mild stress of rats.
Serotonergic receptors take their physiologic effects by affecting adenylyl cyclase (AC) catalytic activity and cyclic adenosine monophosphate (cAMP) concentration. AC-cAMP second messenger pathway has been recently suggested to play an important role in depression. Therefore, the compound that regulates the signal pathway may have potential as antidepressant. Curcumin is the main component of Curcuma longa L, a well-known indigenous herb with comprehensive bioactivities. In the present study, we investigated the effects of chronic unpredictable mild stress (CUMS) and curcumin on behaviours and serotonergic receptor-coupled AC-cAMP signal pathway in rats. Curcumin produced beneficial effects on the stressed rats by effectively improving CUMS-induced low sucrose consumption and reducing serum corticosterone levels in rats. Moreover, curcumin enhanced AC activity and cAMP levels in platelet and various brain regions, and up-regulated mRNA expressions of AC subtypes AC 2, AC 8 and cAMP response element binding protein (CREB) in the hippocampus, cortex and hypothalamus of the CUMS rats. Curcumin also attenuated CUMS-induced reductions of 5-hydroxytryptamine (5-HT) levels and high expressions of central 5-HT(1A/1B/7) receptors in rats. These results suggested that the potent antidepressant property of curcumin might be attributed to its improvement of AC-cAMP pathway as well as CREB via suppressing central 5-HT(1A/1B/7) receptors in the CUMS rats. Our findings provided a basis for examining the interaction of serotonergic receptors and AC-cAMP pathway in depression and curcumin treatment.
Li
Yu-Cheng
YC
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China.
Wang
Fu-Meng
FM
Pan
Ying
Y
Qiang
Li-Qin
LQ
Cheng
Guang
G
Zhang
Wei-Yun
WY
Kong
Ling-Dong
LD
D000262:Adenylyl Cyclases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003474:Curcumin / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005473:Fluoxetine / Q000627:therapeutic use; D005508:Food Deprivation / Q000502:physiology; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects; D014868:Water Deprivation / Q000502:physiology
D000928:Antidepressive Agents; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D005473:Fluoxetine; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003474:Curcumin; D003345:Corticosterone