The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia.
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 beta-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.
Grippo
Angela J
AJ
Department of Psychology, Cardiovascular Center, University of Iowa, Iowa City, Iowa 52242-1407, USA.
Beltz
Terry G
TG
Weiss
Robert M
RM
Johnson
Alan Kim
AK
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004452:Echocardiography; D005473:Fluoxetine / Q000494:pharmacology*; D005518:Food Preferences / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology*; D013395:Sucrose
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D013395:Sucrose