Multiple opioid receptors mediate the hypotensive response induced by central 5-HT3 receptor stimulation

The aim of the present work was to investigate the role of brain mu, kappa and delta opioid receptors in the central serotonergic mechanisms regulating blood pressure in rats. The data obtained show that: (1) pharmacological activation of central 5-HT3 receptors yields a significant decrease in blood pressure; (2) the blockade of those receptors by a selective antagonist induces an acute hypertensive response; (3) the pharmacological blockade of central opioid receptors by three different opioid antagonists exhibiting variable degrees of selectivity to mu, kappa and delta opioid receptors always suppressed the hypotensive response induced by central 5-HT3 receptor stimulation; (4) the blockade of opioid receptors by the same opioid antagonists that impaired the hypotensive effect of central 5-HT3 receptor stimulation failed to modify blood pressure in animals not submitted to pharmacological manipulations of central 5-HT3 receptor function. It is shown that a 5-HT3 receptor-dependent mechanism seems to be part of the brain serotonergic system that contributes to cardiovascular regulation since the hypertensive response observed after ondansetron administration indicates that central 5-HT3 receptors exert a tonic inhibitory drive on blood pressure. Furthermore, the data obtained here clearly indicate that the hypotensive response observed after pharmacological stimulation of central 5-HT3 receptors depends on the functional integrity of brain mu, kappa and delta opioid receptors, suggesting that a functional interaction between serotonergic and opiatergic pathways in the brain is part of the complex, multifactorial system that regulates blood pressure in the central nervous system. (C) 2011 Elsevier Ltd. All rights reserved.