Cardiovascular effects of intrathecal administration of agents active at 5-hydroxytryptamine1-receptors in the rat: modulation by substance P and a substance P antagonist.

The intrathecal (i.th., T8-10) administration in conscious rats of the 5-hydroxytryptamine (5-HT)1A agonist 8-OH-DPAT (10 nmol), and to a lesser extent the 5-HT1B agonist CGS 12066B (6 nmol), resulted in a blood pressure reduction and a bradycardia. These responses were prevented by the i.th. pretreatment with substance P (SP) (6.5 nmol) and enhanced following pretreatment with the non-peptide SP antagonist CP-96,345 (10 nmol). The partial 5-HT1A agonist 8-MeO-CLEPAT (10 nmol) had by itself small cardiovascular effects. Following the pretreatment with SP, 8-MeO-CLEPAT caused a pressor response and a tachycardia whereas the opposite effects were observed following pretreatment with the SP antagonist. These results support the notion of a functional interaction between serotonergic and SP mechanisms at the level of the preganglionic sympathetic nerves in the spinal cord.