The Effects of Chronic Fluoxetine Treatment on Chronic Mild Stress-Induced Cardiovascular Changes and Anhedonia

Abstract

Depression has a complex bidirectional association with heart disease. Previously we have shown notable cardiovascular changes in the chronic mild stress (CMS) rodent model of depression. Here we investigated the effects of a serotonin-specific reuptake inhibitor on a behavioral index of depression (anhedonia) and cardiac function in rats exposed to CMS. Male Sprague-Dawley rats were exposed to either 4 weeks of control conditions or CMS, consisting of unpredictable periods of mild stressors, while being treated concurrently with 4 weeks of daily fluoxetine (10 mg/kg, sc) or vehicle. Chronic fluoxetine treatment prevented anhedonia in rats exposed to CMS, versus the CMS group treated with vehicle. However, treatment with fluoxetine in the CMS group only partially prevented specific cardiovascular changes associated with CMS, including elevated resting heart rate (HR), exaggerated pressor and HR responses to air jet stress, reduced cardiac output and stroke volume, and HR exaggerated responses to beta-adrenergic receptor blockade. These findings provide evidence that 4 weeks of fluoxetine treatment can prevent behavioral responses and can partially prevent cardiovascular changes associated with CMS, providing insight into the role of serotonin in the link between depression and cardiovascular dysfunction.