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.
Vianna
Daniel M L
DM
School of Medical Sciences, Univ. of New South Wales, New South Wales, NSW 2052, Australia. dmvianna@unsw.edu.au
Carrive
Pascal
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003080:Cold Temperature; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D012149:Restraint, Physical / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology / Q000517:prevention & control*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin