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

The dopamine reuptake inhibitor GBR 12909 and the dopamine releaser phenter mine may have potential for the treatment of cocaine abuse in humans. Pre-s ession treatment with either drug can decrease cocaine-maintained respondin g in rhesus monkeys while not affecting food-maintained responding. Both dr ugs are self-administered, but in some reports the patterns of responding t hey maintain differ from typical cocaine-reinforced responding. This study compared self-administration of cocaine (1-100 mug/kg/inj), GBR 12909 (3-10 0 mug/kg/inj), and phentermine (10-170 mug/kg/inj) in rhesus monkeys on a p rogressive-ratio schedule. Individual unit doses of each drug were availabl e across several consecutive sessions. Cocaine self-administration was typi cal: the average number of ratios completed per session was a bitonic (incr easing/decreasing) function of unit dose. Phentermine self-administration w as variable across subjects (two of four monkeys self-administered reliably ); one subject exhibited clear signs of behavioral toxicity. Self-administr ation of GBR 12909 was similarly variable across subjects. In the two subje cts that self-administered GBR 12909 reliably, self-administration of small to mid-sized unit doses was enhanced following exposure to large unit dose s. These data indicate that differences in self-administration of these dru gs can be observed under progressive ratio procedures. Further, the data ad d to existing evidence suggesting that phentermine and GBR 12909 have at le ast moderate potential to be abused by humans. (C) 2001 Elsevier Science Ir eland Ltd. All rights reserved.