Cardiovascular responses produced by microinjection of serotonin-receptor agonists into the paraventricular nucleus in conscious rats.
Activation of serotonin (5-hydroxytryptamine, 5-HT) receptors in the brain produces cardiovascular responses by altering autonomic outflow. The paraventricular nucleus (PVN) contains a modest density of 5-HT receptors and has connections to autonomic centers. Experiments were designed to determine whether cardiovascular responses were produced by the administration of 5-HT2- and 5-HT1A-receptor agonists into the PVN of conscious rats. The microinjection of the 5-HT2-receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] into the PVN produced dose-dependent (1-10 nmol) increases in heart rate and blood pressure; the peak responses were +39 +/- 10 beats/min and +6 +/- 2 mm Hg, respectively. Both responses were blocked by the concomitant administration of the selective 5-HT2-receptor antagonist LY53857 into the PVN. By contrast, the microinjection of the selective 5-HT1A-receptor agonist R(+)-8-OH-DPAT [R(+)8-hydroxy-2-(di-n-propylamino) tetralin HBr; 1-10 nmol] into the PVN did not affect blood pressure or heart rate. These data suggest that 5-HT neurons projecting from the raphe nuclei to or near the PVN can participate in the central control of the cardiovascular system by way of 5-HT2 receptors. Apparently 5-HT neurons terminating in the PVN can increase blood pressure and heart rate and produce sympathoadrenal activation, metabolic and hormonal responses consistent with those observed in several different stress paradigms.
Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas Medical Center, Kansas City 66160-7417, USA.
A A
AA
Bell
B L
BL
Butz
R H
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Alper
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004873:Ergolines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007215:Indophenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C032663:LY 53857