Effects of desipramine maintenance on cocaine self-administration by humans

Six research volunteers with histories of cocaine use were tested in a cocaine choice paradigm to investigate the effects of desipramine maintenance on cocaine-taking behavior. Subjects were allowed to self-administer i.v. saline or cocaine (8, 16 or 32 mg) in daily 3-hr sessions to establish baseline levels of self-administration, self-reported effects of the drug and changes in heart rate and blood pressure. Each subject was then maintained on daily doses of desipramine for 3 to 4 weeks, after which a second cocaine self-administration dose-response curve was generated under desipramine maintenance. This maintenance had no effect on cocaine self-administration. There was, however, a significant increase in heart rate and blood pressure during desipramine maintenance. Desipramine maintenance also resulted in a change in the profile of cocaine's self-reported effects. In some cases (e.g., Arousal and Vigor on the Profile of Mood States, Benzedrine Group scale on the Addiction Research Center Inventory), reports of cocaine's effects were significantly reduced under conditions of desipramine maintenance, and in others (e.g., Anxiety, Anger and Confusion on the Profile of Mood States), those reports were significantly increased. Furthermore, there was a significant decrease in subjects response to an "I want cocaine" question while under desipramine maintenance. The data suggest that desipramine does not affect the reinforcing properties of cocaine, but may interfere with its other stimulus properties. Furthermore, the cardiovascular effects of desipramine appear to have the potential for toxicity when that drug is administered in combination with cocaine.