Hayward Michael D, Pintar John E, Low Malcolm J
The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201, USA.
J Neurosci. 2002 Sep 15;22(18):8251-8. doi: 10.1523/JNEUROSCI.22-18-08251.2002.
It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of beta-endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in beta-endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both beta-endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.
由于这些肽对任何单一阿片受体亚型都没有高度选择性，因此一直无法明确确定哪些内源性阿片类物质调节奖励刺激的激励价值。在此，我们基于对β-内啡肽和脑啡肽基因敲除小鼠的工具性行为测量提出证据，表明这两种阿片肽都发挥着积极作用。采用累进比率程序来测量动物为获得食物强化物而愿意付出多大努力。无论使用的三种不同配方强化物的适口性如何，任何一种阿片类物质的缺失都会降低在此程序下的反应。缺乏两种内源性阿片类物质的小鼠的表型与任何一种单独阿片类物质突变的小鼠的表型几乎相同。在非剥夺和剥夺进食状态下对反应进行了测试，但仅在非剥夺条件下饲养时，β-内啡肽和脑啡肽缺乏的小鼠的反应才会降低。其他操作性操作排除了可能非特异性导致此结果的变量，如习得差异、早期饱腹感、运动性能缺陷和消退抗性降低。与对工具性表现的影响相反，一种或两种内源性阿片类物质的缺失在双瓶自由选择饮水范式中并不影响对蔗糖或糖精调味水的偏好。我们得出结论，β-内啡肽和脑啡肽都对获取食物强化物的激励动机有积极贡献。由于仅在非剥夺动机状态下观察到操作性反应的减弱，进食的享乐主义可能发生了改变，而不是能量稳态。
