Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression

• Published in: PloS one 2017-10, Vol.12 (10), p.e0186700
• Main Authors: Lu, Yanxia, Ho, Cyrus S, Liu, Xin, Chua, Anna N, Wang, Wei, McIntyre, Roger S, Ho, Roger C
• Format: Article
• Language: English
• Subjects: Animals; Antidepressants; Behavior; Biology and Life Sciences; Brain; Brain - metabolism; Chronic effects; Clinical psychology; Complications and side effects; Cytokines; Cytokines - blood; Cytokines - metabolism; Depression (Mood disorder); Depression - drug therapy; Diabetes; Disease Models, Animal; Dosage and administration; Drug therapy; Emotional disorders; Female; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - therapeutic use; Genetic aspects; Health care; Inflammation; Inflammation Mediators - blood; Inflammation Mediators - metabolism; Interleukin 17; Interleukin 6; Medicine; Medicine and Health Sciences; Mental depression; Neurosciences; Physical Sciences; Physiological aspects; Plasma levels; Plasmas (physics); Psychiatry; Psychopharmacology; Public health; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Rodents; Serotonin; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - therapeutic use; Stress; Studies; Sucrose; Sugar; Swimming; Time measurement; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186700

This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p