Cardiovascular responses to cocaine self-administration: acute and chronic tolerance

The nature and the mechanism of tolerance to the cardiovascular responses to cocaine self-administration were studied in rats implanted with telemetric devices. The first infusion of cocaine (1 mg/kg/infusion) on day 1 of testing produced rapid and brief increases in mean arterial blood pressure and in heart rate. Subsequent infusions in the same session produced minimal effects. With chronic testing, there were gradual reductions in cardiovascular responses to the first infusion in the daily session and enhancements in the daily cocaine intake, with significant changes occurring by the fourth week of the testing. Following saline extinction testing (for 5 days), reinstatement of cocaine during week 6 led to a partial and short lasting (