Inhibition of the cardiovascular response to stress by systemic 5-HT1A activation: sympathoinhibition or anxiolysis?

5-HT(1A) 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 whether systemic treatment with a 5-HT(1A) 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 intraperitoneal injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.05 and 0.25 mg/kg), a preferential 5-HT(1A) agonist, or vehicle on the cardiovascular responses to four stressors known to produce sympathetic activation, three being 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 degrees C). The results suggest that 8-OH-DPAT acts preferentially on limbic, rather than central, autonomic sites. Hence, doses of 5-HT(1A) agonists, which are just sufficient to produce anxiolysis, are not enough to cause true sympathoinhibition.