Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sci Rep. 2022 Nov 16;12(1):19683. doi: 10.1038/s41598-022-24173-x.
Progressive ratio (PR) schedules of drug delivery are used to determine the 'motivational' state of an animal and drug 'reinforcing efficacy'. This widely held interpretation is supported mainly by the observation that the PR breakpoint (BP) is proportional to the unit dose of self-administered drug. The compulsion zone theory of cocaine self-administration was applied to determine whether it can explain the pattern of lever-pressing behavior and cocaine injections under the PR schedule in rats. This theory states that cocaine induces lever pressing when levels are below the satiety threshold and above the priming/remission threshold. Rats were trained to self-administer cocaine on a fixed ratio FR1 schedule over a range of cocaine unit doses. Then they were switched to a PR schedule. Typical for the self-administration under a PR schedule, long post-injection pauses occurred when calculated cocaine levels were in the satiety zone. The compulsion zone theory interprets BP simply as the maximal number of responses which rats can perform after an injection while cocaine levels remain within the compulsion zone. The thresholds delineating the compulsion zone were very stable and independent of the self-administration schedule. PR and fixed ratio schedules convey the same pharmacokinetic/pharmacodynamic information, i.e., these two schedules are invariant.
递增比率（PR）药物传递方案用于确定动物的“动机”状态和药物“强化效力”。这种广泛持有的解释主要是基于观察到 PR 断点（BP）与自我给药的药物单位剂量成正比。可卡因自我给药的强制区域理论被应用于确定它是否可以解释大鼠在 PR 方案下的杠杆按压行为和可卡因注射模式。该理论指出，当水平低于饱食阈值且高于启动/缓解阈值时，可卡因会引起杠杆按压。大鼠在一系列可卡因单位剂量下接受固定比率 FR1 方案的可卡因自我给药训练。然后，他们切换到 PR 方案。在 PR 方案下的自我给药中，典型的是当计算出的可卡因水平处于饱食区时，注射后会出现长时间的注射后停顿。强制区域理论简单地将 BP 解释为在可卡因水平保持在强制区域内时，大鼠在注射后可以进行的最大响应次数。划定强制区域的阈值非常稳定，与自我给药方案无关。PR 和固定比率方案传达相同的药代动力学/药效学信息，即这两个方案是不变的。
