Progressive-ratio (PR) schedules of reinforcement have provided valuable information regarding the reinforcing strength of cocaine and the underlying neurobiological mechanisms. Parametric manipulations, such as altering time-out (TO) values, can affect the shape of the cocaine dose-response curve. Earlier studies have used PR schedules with widely varying parameters, thus complicating comparisons across experiments. This study evaluated the reinforcing strength of cocaine (0.005-0.9 mg/kg) as a function of post-reinforcement TO duration (5, 10, 30, or 60 min) under a PR schedule in rhesus monkeys. Daily sessions ended when 2 h elapsed without an injection; the breakpoint value was defined as the total number of injections. When the TO was 10 min, the relationship between cocaine dose and the number of injections received (i.e. BP) was characterized by an inverted U-shaped curve in all monkeys. Increasing the TO to 30 min resulted in a rightward shift of the ascending limb of the dose-response curve, but did not affect self-administration of higher doses. The number of injections received of a low cocaine dose was not further increased when the TO was shortened to 5 min, nor did increasing the TO to 60 min alter self-administration of the highest tested dose. These results suggest that drug accumulation plays a role in determining the reinforcing strength of low and intermediate cocaine doses under PR schedules. However, the reinforcing strength of higher cocaine doses was unaffected by manipulating TO, suggesting that the BP value is a useful measure of reinforcing strength.

译文

渐进比率 (PR) 增强时间表提供了有关可卡因增强强度和潜在神经生物学机制的有价值的信息。参数操作 (例如更改time-out (至) 值) 会影响可卡因剂量反应曲线的形状。早期的研究使用了参数变化很大的PR时间表,因此使实验之间的比较变得复杂。这项研究评估了恒河猴在PR计划下可卡因 (0.005-0.9 mg/kg) 的增强强度与增强后持续时间 (5、10、30或60分钟) 的函数。当2小时过去了而没有注射时,每日疗程结束; 断点值定义为注射总数。当至10分钟时,可卡因剂量与接受的注射次数 (即BP) 之间的关系的特征是所有猴子的U形曲线。增加到30分钟会导致剂量反应曲线的上升肢向右移动,但不会影响较高剂量的自我给药。当将剂量缩短至5分钟时,接受低可卡因剂量的注射次数没有进一步增加,将剂量增加至60分钟也没有改变最高测试剂量的自我给药。这些结果表明,药物积累在确定PR计划下中低可卡因剂量的增强强度中起作用。然而,较高可卡因剂量的增强强度不会受到操纵的影响,这表明BP值是增强强度的有用度量。

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