INHIBITION OF THE CARDIOVASCULAR RESPONSE TO STRESS BY SYSTEMIC 5-HT1A ACTIVATION: SYMPATHOINHIBITION OR ANXIOLYSIS?

Abstract

5-HT1A agonists given systemically are known to produce anxiolytic effects. In addition, a growing body of research is showing that those compounds also have central sympathoinhibitory properties. Since emotional arousal gives rise to sympathetic activation, it is not clear if systemic treatment with a 5-HT1A agonist reduces the sympathetic response to emotional stress primarily by a direct action on sympathetic-related sites in the brain or indirectly through reducing anxiety. To test this, we compared the effect of i.p. injections of 8-OH-DPAT (0.05 and 0.25 mg/kg), a preferential 5-HT1A agonist, or vehicle, on the cardiovascular responses to four stressors known to produce sympathetic activation, three of them emotional stressors, and one physiological. In conscious rats, 30 min exposure to either a neutral context, a fear-conditioned context or to restraint stress led to increases in heart rate and blood pressure, which were attenuated by 8-OH-DPAT. In contrast, the same treatment did not reduce the cardiovascular response to 30 min cold exposure (4°C). The results suggest that 8-OH-DPAT acts preferentially on limbic, rather than central autonomic sites. Hence, doses of 5-HT1A agonists which are just sufficient to produce anxiolysis are not enough to cause true sympathoinhibition.