Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD 21224-6823, USA.
Addict Biol. 2012 Sep;17(5):887-96. doi: 10.1111/j.1369-1600.2011.00335.x. Epub 2011 Jul 18.
A relatively small percentage of humans who are exposed to drugs of abuse eventually become addicted to or dependent on those drugs. These individual differences in likelihood of developing drug addiction may reflect behavioral, neurobiological or genetic correlates of drug addiction and are therefore important to model. Behavioral economic measures of demand establish functions whose overall elasticity (rate of decrease in consumption as price increases) reflects the reinforcing effectiveness of various stimuli, including drugs. Using these demand functions, we determined the reinforcing effectiveness of five drugs of abuse (cocaine, remifentanil, ketamine, methohexital and ethanol) in 10 rhesus monkeys with histories of intravenous drug-taking. There was a continuum of reinforcing effectiveness across the five drugs, with cocaine and remifentanil showing the most reinforcing effectiveness. There was also a continuum of sensitivity of the monkeys; two of the 10 animals, in particular, showed greater demand for the drugs than did the remaining eight monkeys. In addition, monkeys that demonstrated greater demand for one drug tended to show greater demand for all drugs but did not show a similar relatively greater demand for sucrose pellets. These findings suggest that the tendency to find drugs to be reinforcing is a general one, not restricted to particular drugs and also, that a minority of animals show a substantially enhanced sensitivity to the reinforcing effects of drugs. The possibility that differences in responsiveness to the reinforcing effects of drugs may form the basis of individual differences in drug-taking in humans should be considered.
只有一小部分接触过滥用药物的人最终会对这些药物上瘾或依赖。这些个体在成瘾可能性上的差异可能反映了成瘾的行为、神经生物学或遗传相关性，因此建模这些差异很重要。需求的行为经济学测量建立了功能，其整体弹性（随着价格增加消费减少的速度）反映了各种刺激物（包括药物）的强化效果。使用这些需求函数，我们确定了 10 只有静脉吸毒史的恒河猴对五种滥用药物（可卡因、瑞芬太尼、氯胺酮、美索比妥和乙醇）的强化效果。这五种药物的强化效果呈连续变化，可卡因和瑞芬太尼的强化效果最强。猴子的敏感性也呈连续变化；这 10 只动物中有两只，特别是比其他 8 只猴子对药物有更高的需求。此外，对一种药物表现出更高需求的猴子往往对所有药物都表现出更高的需求，但对蔗糖丸却没有表现出类似的相对较高的需求。这些发现表明，寻找药物有强化作用的倾向是普遍存在的，不仅限于特定的药物，而且少数动物对药物的强化作用表现出明显更高的敏感性。应该考虑到，对药物强化作用的反应差异可能是人类药物使用个体差异的基础。
