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

This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antide-pressant, on the peripheral and central levels of inflammatory cytokines including IL-1 beta, IL6, TNF-alpha 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-1 beta, IL-17, and TNF-alpha on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1 beta in plasma and brain after 90 and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL-6 and TNF-alpha concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1 beta in the alleviation of depressive symptoms.