The cardiovascular effects of amperozide: interactions with cocaine.

Abstract

Amperozide is a 5-HT2A receptor antagonist that significantly reduces the acquisition and expression, by rats, of a cocaine conditioned place preference. In order to rule out the possibility that amperozide affects a cocaine conditioned place preference due to effects on blood pressure or heart rate, the cardiovascular effects of amperozide were investigated. Alternating cumulative doses of amperozide (0.5, 1.0, 1.5 and 2.5 mg kg(-1)) or saline and phenylephrine (8 microg kg(-1)) were administered through the femoral vein of awake freely-moving Sprague-Dawley rats and blood pressure and heart rate were recorded from the femoral artery. A single dose of cocaine (5.0 mg kg(-1)) was administered after all the amperozide or saline doses were given. Amperozide (0.5, 1.0, 1.5 and 2.5 mg kg(-1)) did not have any significant effect on blood pressure compared to the saline control treatment to the same animals. However, 0.5 mg kg(-1) amperozide significantly decreased heart rate at 5 and 10 min. after administration. but higher doses did not further depress heart rate. Amperozide did not affect the increased blood pressure and decreased heart rate caused by phenylephrine. an alpha1-adrenoceptor agonist. In addition, amperozide did not affect the cardiovascular response to an intravenous dose of 5.0 mg kg(-1) cocaine. These results suggest that amperozide does not cause direct cardiovascular effects. The mechanism by which the lowest dose of amperozide caused a decrease in heart rate is unknown. Amperozide affects neither alpha-adrenoceptor mediated vasoconstriction nor the increased sympathetic activity caused by the peripheral and central effects of cocaine. The significance of these results, in terms of locomotor activity and the cocaine conditioned place preference paradigm, is discussed.