EFFECTS OF DELIVERY RATE AND NONCONTINGENT INFUSION OF COCAINE ON COCAINE SELF-ADMINISTRATION IN RHESUS-MONKEYS

The goal of this study was to determine whether slowly infused, respon se-independent cocaine would reduce cocaine self-administration in an animal model of drug abuse. Seven male rhesus monkeys self-administere d IV cocaine on a fixed-ratio 30 schedule (5-min time-out). With unit dose (0.056 mg/kg per infusion for one monkey and 0.032 mg/kg per infu sion for the rest) and infusion volume (0.5 mi) held constant, the rat e of delivery was manipulated (0.125, 0.1875, 0.375, 0.75 and 3 ml/min , with infusions lasting 240, 160, 80, 40, and 10 s, respectively). Re sponse rates increased monotonically as a function of delivery rate. R esponding for cocaine at the slowest delivery rate did not differ from saline. The effects of infusing additional cocaine (starting 30 min p rior to the session) at this non-reinforcing rate (0.125 ml/min) were then determined. Delivery rate of the self-administered infusion was m anipulated as before. Non-contingent cocaine significantly increased r esponding for cocaine (at the fastest delivery rate) and for saline. W hile non-contingent cocaine reduced responding for cocaine in two of t he seven monkeys, it also significantly reduced responding in three mo nkeys that responded for food on the same schedule. Plasma levels of c ocaine delivered at rates of 0.125 and 3 ml/min were compared in five other monkeys. While a higher peak was reached with the faster infusio n, levels did not differ after 5 min. Thus, when an infusion became av ailable (after the fi-min time-out) in the self-administration experim ents, plasma levels should not have differed regardless of the deliver y rate. These results suggest that a low-dose, slow-delivery treatment with cocaine might prime or reinstate drug seeking rather than decrea se it.