title: Escitalopram reduces circulating pro-inflammatory cytokines and improves depressive behavior without affecting sleep in a rat model of post-cardiac infarct depression.
abstract: Myocardial infarction (MI) in rats is followed by a behavioral syndrome similar to human post-MI depression. We tested the effects of escitalopram, a selective serotonin reuptake inhibitor, on this syndrome. MI was induced in 19 Sprague-Dawley rats by occluding the left anterior descending coronary artery for 40min, followed by reperfusion. A sham-operated group of 20 rats was submitted to the same protocol without coronary artery occlusion. Fifteen minutes after the onset of reperfusion, escitalopram (10mg/kg/day, i.p.) or saline was infused continuously through osmotic minipumps. After 2weeks of treatment, the rats were tested for behavioral despair and anhedonia by the forced swimming and sucrose preference tests, respectively. They were then sacrificed, and blood levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), PGE(2) and corticosterone were measured. In a separate cohort of 24 rats, sleep was recorded after 2weeks of post-MI treatment with escitalopram or saline. In MI rats, behavioral despair and anhedonia were blocked by escitalopram but prolonged sleep latency, low total sleep time and short latency to paradoxical sleep (PS) were not; escitalopram decreased PS in sham controls. Plasma TNF-α, PGE(2), and corticosterone levels were higher in MI rats than in the controls. Escitalopram lowered TNF-α, IL-1β, and PGE(2) levels in both groups of rats while IL-6 showed no differences whatsoever. Escitalopram reverses post-MI behavioral syndrome in rats through a mechanism that could involve a reduction of pro-inflammatory cytokines and PGE(2). It has limited effects on sleep disorders in MI rats but reduces PS in control rats.
authors.affiliation: Centre de Biomédecine, Hôpital du Sacré-Cœur de Montréal, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Thierno Madjou
authors.initials: TM
authors.lastname: Bah
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
authors.forename: Sévan
authors.initials: S
authors.lastname: Kaloustian
authors.forename: Ramy
authors.initials: R
authors.lastname: Karam
authors.forename: Guy
authors.initials: G
authors.lastname: Rousseau
authors.forename: Roger
authors.initials: R
authors.lastname: Godbout
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016207:Cytokines; D013549:Sweetening Agents; D015283:Citalopram; D013395:Sucrose