Marked increases in plasma catecholamine concentrations precede hypotension and bradycardia caused by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious rats

Abstract

Plasma noradrenaline and adrenaline responses to 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a selective putative 5-HT1A receptor agonist, have been studied in conscious, freely moving rats. Intravenously administered 8-OH-DPAT caused dose-related and sustained increases in plasma noradrenaline (2-fold) and adrenaline (11-fold) concentrations. Neither metergoline pretreatment (0.5 mg kg-1 i.v.) nor splanchnicectomy had any effect on the noradrenaline and adrenaline elevation caused by 8-OH-DPAT (250 micrograms kg-1 i.v.). The catecholamine responses peaked early but were still present during nadirs in blood pressure and heart rate. The discrepancy between plasma catecholamine and cardiovascular changes raises further questions about the mechanism of action of 8-OH-DPAT and supports other evidence suggesting a role for vagus stimulation in the cardiovascular effects caused by this drug.