A comparison of cocaine, GBR 12909, and phentermine self-administration by rhesus monkeys on a progressive-ratio schedule

Abstract

The dopamine reuptake inhibitor GBR 12909 and the dopamine releaser phentermine may have potential for the treatment of cocaine abuse in humans. Pre-session treatment with either drug can decrease cocaine-maintained responding in rhesus monkeys while not affecting food-maintained responding. Both drugs are self-administered, but in some reports the patterns of responding they maintain differ from typical cocaine-reinforced responding. This study compared self-administration of cocaine (1–100 μg/kg/inj), GBR 12909 (3–100 μg/kg/inj), and phentermine (10–170 μg/kg/inj) in rhesus monkeys on a progressive-ratio schedule. Individual unit doses of each drug were available across several consecutive sessions. Cocaine self-administration was typical: the average number of ratios completed per session was a bitonic (increasing/decreasing) function of unit dose. Phentermine self-administration was variable across subjects (two of four monkeys self-administered reliably); one subject exhibited clear signs of behavioral toxicity. Self-administration of GBR 12909 was similarly variable across subjects. In the two subjects that self-administered GBR 12909 reliably, self-administration of small to mid-sized unit doses was enhanced following exposure to large unit doses. These data indicate that differences in self-administration of these drugs can be observed under progressive ratio procedures. Further, the data add to existing evidence suggesting that phentermine and GBR 12909 have at least moderate potential to be abused by humans.