title: The effect of citalopram on chronic stress-induced depressive-like behavior in rats through GSK3β/β-catenin activation in the medial prefrontal cortex.
abstract: Antidepressant treatments enhance synaptic connectivity in stress-sensitive brain regions such as the medial prefrontal cortex (mPFC). The mPFC plays a key role in controlling cognition and emotion. While several signaling pathways are involved in this enhancement process, the exact mechanisms are not fully established. In the present study, we evaluated the role of the glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway in the antidepressant effect of citalopram in rats exposed to forced swim stress. The acute stress group received the classic, two-day variant of the forced swimming test (FST), whereas the chronic stress group received swim stress for 14 consecutive days. We found that rats exposed to acute swim stress showed depressive-like behaviors and expressed normal GSK3β and β-catenin levels in the mPFC. Chronic swim stress, also induced a significant behavior changes but was associated with decreased levels of phosphorylated GSK3β and β-catenin in the rat's mPFC. Chronic citalopram treatment alleviated these behavioral changes in chronically stressed rats and normalized the downregulation of GSK3β/β-catenin signaling. Our results suggest that GSK3β/β-catenin signaling plays an important role in chronic but not acute stress-related depression and contributes, at least in part, to the antidepressant effects of citalopram in distinct brain regions associated with mood regulation.
authors.affiliation: Department of Psychosomatics, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chen
authors.forename: Q R
authors.initials: QR
authors.lastname: Tan
authors.forename: W
authors.initials: W
authors.lastname: Dang
authors.forename: H N
authors.initials: HN
authors.lastname: Wang
authors.forename: R B
authors.initials: RB
authors.lastname: Zhang
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: Liu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D051176:beta Catenin; D015283:Citalopram; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3