Serotonergic mechanisms have an important function in the central control of
circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake
inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in
rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects,
it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy
male Wistar rats were anesthetized with urethane and instrumented to record blood
pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory
frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine
and sertraline administered intravenously were insignificant and variable. At middle
and higher doses, a general pattern was observed, with significant reductions in
sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by
-33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg
paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in
blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without
changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted
approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a
reduction in heart rate that was nearly parallel to the sympathoinhibition. The
effect of these drugs on the other variables was insignificant. In conclusion, acute
peripheral administration of SSRIs caused early autonomic cardiovascular effects,
particularly sympathoinhibition, as measured by RSNA. Although a peripheral action
cannot be ruled out, such effects are presumably mostly central.
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