Elsevier

Biological Psychiatry

Volume 59, Issue 4, 15 February 2006, Pages 309-316
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2005.07.010Get rights and content

Background

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.

Methods

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.

Results

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 β-adrenergic receptor blockade.

Conclusions

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.

Section snippets

Animals

Twenty-four male Sprague-Dawley rats (Harlan, Indianapolis, Indiana), weighing 250–350 g, were used for the experimental procedures. Rats were allowed 1 week to acclimate before beginning experimentation. Animals were housed in individual plastic cages with bedding. Food (Purina Rat Chow 5012; Purina Mills, Brentwood, Missouri) and tap water were available ad libitum for the duration of the experiments unless otherwise noted. Sucrose solution (1%) was available ad libitum for 1 week preceding

Sucrose Preference Tests

Figure 2 presents water (Panel A) and sucrose (Panel B) intake in CMS+FL, CMS+V, CON+FL, and CON+V groups at baseline and during 4 weeks of CMS. Chronic mild stress produced a significant decline in sucrose intake, and animals in this group treated with fluoxetine showed intakes that were comparable to the control groups after 4 weeks of CMS. Neither CMS nor fluoxetine treatment affected water intake after 4 weeks of CMS. Data from water and sucrose intake were analyzed separately with

Discussion

It is not only important to understand the bidirectional association between depression and heart disease, but also to develop pharmacological treatments for depressed cardiac patients that do not impair (and more desirably, improve) cardiovascular status. Although tricyclic antidepressants have useful antidepressant properties, they lead to increased HR, reduced intraventricular cardiac conduction, and orthostatic hypotension (see Roose and Spatz 1999). The cardiotoxic side effects of these

References (51)

  • A. Nosjean et al.

    Increased sympathetic nerve discharge without alteration in the sympathetic baroreflex response by serotonin3 receptor stimulation in the nucleus tractus solitarius of the rat

    Neurosci Lett

    (1995)
  • B. Rudisch et al.

    Epidemiology of comorbid coronary artery disease and depression

    Biol Psychiatry

    (2003)
  • Y.I. Sheline et al.

    How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease

    Am J Med

    (1997)
  • M.J. Sole et al.

    The identification of specific serotonergic nuclei inhibited by cardiac vagal afferents during acute myocardial ischemia in the rat

    Brain Res

    (1983)
  • M. Tatsumi et al.

    Pharmacological profile of antidepressants and related compounds at human monoamine transporters

    Eur J Pharmacol

    (1997)
  • P. Willner et al.

    Chronic mild stress-induced anhedoniaA realistic animal model of depression

    Neurosci Biobehav Rev

    (1992)
  • R. Anda et al.

    Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults

    Epidemiology

    (1993)
  • J.C. Barefoot et al.

    Symptoms of depression, acute myocardial infarction, and total mortality in a community sample

    Circulation

    (1996)
  • Preliminary reportEffect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction

    N Engl J Med

    (1989)
  • R.M. Carney et al.

    Major depressive disorder predicts cardiac events in patients with coronary artery disease

    Psychosom Med

    (1988)
  • S. Cheeta et al.

    Stereospecific reversal of stress-induced anhedonia by mianserin and its (+)-enantiomer

    Psychopharmacology

    (1994)
  • J. Francis et al.

    Progression of heart failure after myocardial infarction in the rat

    Am J Physiol Regul Integr Comp Physiol

    (2001)
  • N. Frasure-Smith et al.

    Depression and other psychological risks following myocardial infarction

    Arch Gen Psychiatry

    (2003)
  • N. Frasure-Smith et al.

    Gender, depression, and one-year prognosis after myocardial infarction

    Psychosom Med

    (1999)
  • F. Fumeron et al.

    Serotonin transporter gene polymorphism and myocardial infarctionEtude Cas-Temoins de l’Infarctus du Myocarde (ECTIM)

    Circulation

    (2002)
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