Citalopram alleviates chronic stress induced depression-like behaviors in rats by activating GSK3β signaling in dorsal hippocampus.
Aside from monoamine disturbances, recent evidence has implicated particular intracellular pathways, including Wnt signaling, in the pathogenesis of major depressive disorder. In the present study, we investigated the role of Wingless (Wnt)-Dishevelled (DVL)-glycogen synthase kinase 3β (GSK3β) signaling in the depression-like behaviors exhibited by rats exposed to chronic forced swim stress. We found that the rats subjected to forced swim stress for 14 consecutive days exhibited obvious depression-like behaviors and showed decreased levels of phosphorylated GSK3β and β-catenin in the hippocampus. Chronic citalopram treatment alleviated the depression-like behaviors and reversed the disruptions of the phosphorylated GSK3β and β-catenin in stressed rats. Furthermore, when the stressed rats with citalopram treatment received bilateral, dorsal hippocampus infusions of a DVL inhibitor, sulindac, the depression-like effects induced by chronic stress reappeared. These findings suggest that the Wnt-DVL-GSK3β signaling in the hippocampus is markedly involved in the pathophysiology of depression induced by chronic stress. The Wnt-DVL-GSK3β pathway may mediate the therapeutic action of citalopram, and the manipulation of DVL could be a target for novel antidepressants.
Department of Geriatrics, Tangdu hospital, Fourth Military Medical University, No. 1 Xinsi Road, Baqiao District, Xi'an, 710032, PR China.
Rui
R
Liu
Wei
W
Dang
Miao
M
Jianting
Changjun
C
Su
Huaning
H
Wang
Yunchun
Y
Chen
Qingrong
Q
Tan
D059445:Anhedonia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013238:Stereotaxic Techniques; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D013467:Sulindac / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D051176:beta Catenin / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015283:Citalopram; D038362:Glycogen Synthase Kinase 3; D017367:Selective Serotonin Reuptake Inhibitors; D013467:Sulindac; D051176:beta Catenin