Efeitos da administração aguda de fluoxetina e paroxetina sobre parâmetros cardiorrespiratórios e autonômicos em ratos anestesiados

Abstract

The activation of central serotonergic receptors is involved in the neural control of cardiovascular system. Selective serotonin reuptake inhibitors are widely used in medicine, and due to their relevance, this study aims to examine the effects of acute administration of two examples of this class of antidepressants, fluoxetine and paroxetine, on cardiorespiratory and autonomic parameters in rats. We used male Wistar rats, 250-300 g, anesthetized with urethane (1.2 g/kg, i.v.) instrumented for recording mean blood pressure (BP), heart rate (HR), respiratory frequency (RF) and sympathetic renal nerve activity (RNA). The animals received the drug in doses of 1, 3 or 10 mg/kg intravenously. The statistical significance of the difference between the means was assessed by ANOVA followed by appropriate multiple comparisons tests. When comparing the group of animals that received fluoxetine with the control animals, it was observed that fluoxetine at a dose of 1 mg/kg showed no statistically significant differences in any parameter measured, but at a dose of 3 mg/kg promoted an sympathoinhibition in all the times of the trial, while in fluoxetine 10 mg/kg promoted a decrease of HR at the time of 5 minutes and the ANR in times of 5, 20, 30 and 50 minutes. Fluoxetine showed a dose-effect pattern on the ANR. The administration of paroxetine at a dose of 1 mg/kg only caused a decrease in the ANR at the time of 5, 15, 20 and 50 minutes, and at a dose of 3 mg/kg determined sympathoinhibition, which occurred in all experimental times, but at a dose of 10 mg/kg, developed an increase in MAP and a sympathoinhibition at all experimental times, a tachycardia starting from the 20 minutes on. Paroxetine induced an important dose-effect response for MAP, HR and ANR. These results suggest that the SSRIs exert their changes in cardiorespiratory and autonomic parameters through activation of serotonergic receptors in different locations in the CNS. We hypothesize that the fluoxetine response appears to involve more 5-HT1A receptors in the dorsal raphe, raphe magnus, raphe pallidus or RVLM, whist paroxetine appears to activate 5-HT1A receptors in various locations in the brain, as in the raphe obscurus and pre-optica area, in addition to the dorsal raphe, raphe magnus, raphe pallidus or RVLM, therefore triggering different responses.