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

:增强的渐进比率(PR)计划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(例如更改超时(TO)值)可能会影响可卡因剂量反应曲线的形状。较早的研究使用的PR计划参数各不相同,因此使整个实验的比较变得复杂。这项研究评估了在猕猴的PR计划下,可卡因的增强强度(0.005-0.9 mg / kg)与增强后TO持续时间(5、10、30或60分钟)的关系。每天的会议在没有注射2小时后结束;断点值定义为进样总数。当TO为10分钟时,可卡因剂量与所接受的注射次数(即BP)之间的关系以所有猴子的倒U形曲线为特征。将TO增加到30分钟会导致剂量反应曲线的上升肢向右移动,但不会影响大剂量的自我给药。当TO缩短至5分钟时,低可卡因剂量的注射次数没有进一步增加,TO升高至60分钟也没有改变最高试验剂量的自我给药。这些结果表明,在PR计划下,药物蓄积在确定中低剂量可卡因的增强强度中起着作用。但是,可卡因剂量的增强强度不受操作TO的影响,表明BP值是增强强度的有用指标。

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