Centrally mediated hemodynamic effects of cocaine in rabbits: the role of local anesthetic actions and biogenic amine re-uptake blockage.

ABSTRACT

This study sought to identify the central nervous system-mediated cardiovascular effects of cocaine and to determine if these effects result from local anesthetic action or biogenic amine re-uptake blockade. New Zealand rabbits received multiple i.c.v. doses of cocaine, pseudococaine, lidocaine or desipramine while recording blood pressure and heart rate. Moderate dose cocaine produced a decrease in heart rate and mean arterial pressure while the highest dose produced increases in heart rate and blood pressure. Lidocaine and pseudococaine produced dose-dependent increases in blood pressure while desipramine produced decreases in heart rate and mean arterial pressure. In this model, the central nervous system-mediated cardiovascular effects of cocaine are dose-dependent; low doses produced cardiovascular depression while higher doses produced cardiovascular stimulation. The data also suggest that cocaine's local anesthetic effects are responsible for its central nervous system-mediated cardiovascular stimulation, while biogenic amine re-uptake blockade causes cardiovascular depression.