Central Nervous Actions of Serotonin and a Serotonin.A Receptor Agonist: Cardiovascular Excitation at Low Doses1

Studies were performed in conscious unrestrained rats to corn-pare the cardiovascular effects of i.c.v. administration of sero-tonin (5-HT) and the 5-HTIA receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Low doses (<1 0 nmol) of 5-HT and 8-OH-DPAT eliCited significant elevations of artetial pressure and heart rate. At doses greater than 1 0 nmol, 5-HT produced pressor responses attended by significant reductions of heart rate whereas 8-OH-DPAT produced significant depres-sor and bradycardic responses. Concurrent i.c.v. administration ofthe nonselective 5-HT receptor antagonist, methiothepin, abol-ished the cardiovascular responses to a low (1 nmol) and a high (1 00 nmol) dose of 5-HT and a low (3 nmol) dose of 8-OH-DPAT. In contrast, methiothepin cotreatment did not prevent the reduc-tions of arterial pressure and heart rate induced by a high (100 nmol) dose of 8-OH-DPAT. These results suggest that stimula-tion of central nervous system 5-HT1A receptors with low doses of 8-OH-DPAT produces cardiovascular activation. Neuroanatomic, physiologic and pharmacologic data support the notion that CNS 5-HT-containing pathways participate in governing autonomic nervous activity and cardiovascular func-tion (McCall, 1988). The regulatory role of such pathways is quite complex as underscored by both electrophysiologic and pharmacologic studies. Thus, activation of 5-HT-containing neurons is demonstrated to elicit both excitatory and inhibitory effects on sympathetic nervous activity and arterial pressur