Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Abstract

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.

Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice

“…Pretreatments of the selective SERT inhibitor fluoxetine (3 mg/kg), the NET-preferring inhibitor desipramine (3 mg/kg), the DAT-preferring inhibitor bupropion (10 mg/kg), or saline, occurred 30 minutes before administration of 10 mg/kg MDPV. The pretreatment doses used in the present study were the largest doses we tested that were within the dosing ranges used in the literature to selectively block monoamine reuptake (e.g., Eriksson et al, 2011; Fish et al, 2004; Klevin and Koek, 1998; Shen et al, 2013; Tiradentes et al, 2014; Valentini et al, 2006). Data obtained using smaller doses of the pretreatment compounds produced no effects on any of the endpoints examined (data not shown), and larger doses of the pretreatment compounds were not used in the present study because transporter selectivity would be unlikely to be maintained.…”

Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence

“…However, the mechanism whereby beta 1-adrenergic upregulation in ischemic-brain regions might improve recovery remains to be answered. Additionally, another study in rats demonstrated that acute peripheral administration of SSRIs induces changes in autonomic cardiovascular function mediated by inhibition of sympathetic activity, presumably via a central mechanism (Tiradentes et al 2014). However, it remains speculative whether SSRI-induced central sympathoinhibition and consecutive changes in autonomic cardiovascular function (such as increase in heart rate variability or improved vasomotor reactivity) might contribute to post stroke recovery or have beneficial effects on prevention of recurrent cardiovascular events in humans.…”

How do the Psychosocial Factors Affect Blood Pressure in Patients with Hypertension? A Cross-Sectional Study

“…Fluoxetine and sertraline, but not paroxetine, cause a reduction in heart rate that was nearly parallel to the sympatho-inhibition. In the same research, fluoxetine and sertraline did not increase blood pressure [19,20].…”