Sevak Rajkumar J, Stoops William W, Glaser Paul E A, Hays Lon R, Rush Craig R
aDepartments of Behavioral Science bPsychiatry cAnatomy and Neurobiology dPediatrics, College of Medicine ePsychology, College of Arts and Science, University of Kentucky, Lexington, Kentucky.
Behav Pharmacol. 2010 Dec;21(8):745-53. doi: 10.1097/FBP.0b013e32833fa7b3.
Progressive-ratio schedules are useful for studying the reinforcing effects of drugs. Earlier human laboratory studies showed that d-amphetamine significantly increased break points relative to placebo. However, the magnitude of the increase was modest, which may be attributable to rather high levels of placebo responding. We used novel response requirements in a modified progressive-ratio procedure and hypothesized that the altered range of response requirements would decrease responding for placebo and increase responding for d-amphetamine. Eight participants completed the study. The participants first sampled oral doses of d-amphetamine (0, 8, 16, and 24 mg). In subsequent sessions, the participants were offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure with response requirements ranging from 400 to 1800 mouse clicks. A battery of participant-rated drug-effect questionnaires, a performance measure, and cardiovascular measures were included to more fully characterize the effects of d-amphetamine. Placebo maintained low levels of responding. The intermediate dose of d-amphetamine increased responding significantly above placebo levels. d-Amphetamine produced prototypical subject-rated effects that were an orderly function of dose. These data suggest that the modified response requirements resulted in lower levels of placebo taking and a larger separation between the number of placebo and d-amphetamine capsules earned.
累进比率程序对于研究药物的强化作用很有用。早期的人体实验室研究表明，相对于安慰剂，右旋苯丙胺显著提高了断点。然而，增加的幅度较小，这可能归因于安慰剂反应水平相当高。我们在改良的累进比率程序中使用了新的反应要求，并假设反应要求范围的改变会减少对安慰剂的反应，增加对右旋苯丙胺的反应。八名参与者完成了这项研究。参与者首先口服了不同剂量的右旋苯丙胺（0、8、16和24毫克）。在随后的实验中，参与者有机会在改良的累进比率程序中为所服用的剂量而工作，反应要求范围为400至1800次鼠标点击。还纳入了一系列参与者评定的药物效应问卷、一项表现测量指标和心血管测量指标，以更全面地描述右旋苯丙胺的效应。安慰剂维持了较低的反应水平。右旋苯丙胺的中等剂量使反应显著高于安慰剂水平。右旋苯丙胺产生了典型的、与剂量呈有序函数关系的受试者评定效应。这些数据表明，改良的反应要求导致了较低的安慰剂服用水平，以及所获得的安慰剂胶囊数量与右旋苯丙胺胶囊数量之间更大的差距。
