Cocaine remains a major public health concern due to a continuing increase in the number of emergency room admissions following cocaine use. Cardiovascular complications represent a large proportion of these admissions. Cardiovascular effects of cocaine are being extensively studied using various species of animals as model systems. Recent research has focused on the influence of conditioning on the cardiovascular effects of cocaine. Most human drug abusers consistently use cocaine in the same environment. It is possible that the cardiovascular effects of cocaine could become conditioned to that environment to either augment or counteract those effects. In squirrel monkeys, cocaine injections were consistently paired with a tone-light conditioned stimulus. By the third stimulus-cocaine pairing, a conditioned response was observed that was drug-like. That is, the conditioned response to the tone-light stimulus was similar to the unconditioned effect of cocaine in that both heart rate and blood pressure were increased. This effect may serve to augment the cardiovascular effects of cocaine. The conditioned response was also long lasting. After 10 conditioning trials, the cocaine injections were stopped (extinction). In one monkey, a response to the conditioned stimulus that was above baseline levels was still observed after 30 extinction trials. These results suggest that the conditioned cardiovascular effects of cocaine may well contribute to some of the adverse effects seen following cocaine administration. In other studies, cardiovascular responses to chronic limited access (2 hr/day) cocaine self-administration were studied in Sprague-Dawley rats implanted with telemetric devices. Following training to lever press for food, rats were tested for cocaine (1 mg/kg/infusion) self- administration for four weeks, followed by extinction with saline during week 5, and then re-testing of cocaine self-administration during week 6. The first infusion of cocaine within a given session produced rapid (less then 60 sec) increases in diastolic, systolic and mean pressures and in heart rate (HR). The subsequent cocaine infusions within the same session produced increases in pressures that were significantly smaller than that of the first infusion and failed to increase HR. These patterns of responses were seen on all days of testing, however, the mean increases in pressures and HR produced by the first infusions during the daily sessions of weeks 4 and 6 were significantly smaller as compared to the corresponding increases seen during the first week of testing. These data indicate that there are two kinds of tolerance to pressor and tachycardiac responses to cocaine. One is an acute tolerance, which occurs within each session following a single infusion of cocaine, while the other is a chronic tolerance which occurs over several weeks of cocaine self- administration.
