Stafford D, LeSage M G, Rice K C, Glowa J R
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Drug Alcohol Depend. 2001 Mar 1;62(1):41-7. doi: 10.1016/s0376-8716(00)00158-7.
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 microg/kg/inj), GBR 12909 (3--100 microg/kg/inj), and phentermine (10--170 microg/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.
多巴胺再摄取抑制剂GBR 12909和多巴胺释放剂芬特明可能具有治疗人类可卡因滥用的潜力。在实验前用这两种药物中的任何一种进行治疗，均可降低恒河猴对可卡因维持的反应，而不影响对食物维持的反应。这两种药物都可被自我给药，但在一些报告中，它们维持的反应模式与典型的可卡因强化反应不同。本研究在恒河猴身上采用累进比率程序比较了可卡因（1--100微克/千克/注射）、GBR 12909（3--100微克/千克/注射）和芬特明（10--170微克/千克/注射）的自我给药情况。每种药物的个体单位剂量在连续几个实验时段内都可获得。可卡因的自我给药是典型的：每个实验时段完成的比率平均数是单位剂量的双调（先增加后减少）函数。芬特明的自我给药在不同个体间存在差异（四只猴子中有两只能可靠地自我给药）；一只猴子表现出明显的行为毒性迹象。GBR 12909的自我给药在不同个体间也同样存在差异。在两只能可靠地自我给药GBR 12909的猴子中，在接触大单位剂量后，中小单位剂量的自我给药有所增加。这些数据表明，在累进比率程序下可以观察到这些药物自我给药的差异。此外，这些数据进一步证明了芬特明和GBR 12909至少有中等程度的被人类滥用的可能性。
