Acute tolerance to the cardiovascular effects of volatilized cocaine free base in rats.

The cardiovascular effects elicited by volatilized cocaine were compared to those produced by i.v. drug administration. All of the subjects exposed to volatilized cocaine exhibited an initial increase in mean arterial pressure (MAP), profound bradycardia, and heart blocks. Intravenous administration of cocaine (1.5 mg/kg i.v.), a dose equivalent to the amount of drug subjects received from inhalation exposure, led to a transient increase in MAP but failed to produce any obvious ECG abnormalities or bradycardia; however, increasing the dose to 4.5 mg/kg resulted in considerable toxicity. Finally, the hemodynamic effects elicited by inhalation cocaine were found to undergo rapid tolerance during the first 5-min exposure period and the three subsequent drug exposures.