Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, zolpidem, and imidazenil in baboons
Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, zolpidem, and imidazenil in baboons
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DOI：
10.1007/s00213-002-1076-4
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发表时间：
2002-10-01
影响因子：
3.4
通讯作者：
Ator, NA
中科院分区：
文献类型：
--
作者：
Ator, NA
理由：如果一种精神活性药物与另一种维持自我给药的药物具有区别作用，通常可以推断，测试药物很可能是自我给药的，并且有滥用的可能。然而，这种假定的预测关系尚未得到直接研究。目的：在个体水平上确定(1)与强化药物剂量具有区别效应的新药物剂量是否也会作为强化剂；(2)药理学上与训练药物相似的药物的泛化试验结果是否可以预测被试药物是否会自我给药。方法：训练狒狒区分咪达唑仑（0.32 mg/kg，静脉注射）和生理盐水，并进行静脉注射药物强化。在自我给药期开始时，第一次自我注射10分钟后进行药物鉴别测试。然后狒狒有机会每天24小时（每次注射后3小时）自行注射相同剂量的药物。在最后一次自我注射后进行第二次药物鉴别试验。结果：唑吡坦、咪唑西尼与咪唑安定具有相同的鉴别作用。唑吡坦对所有狒狒都有强化作用，但咪唑西尼没有。氯二氮环氧化物与咪达唑仑具有部分鉴别作用，且自我给药率较低。戊巴比妥与咪达唑仑没有区别作用，但有强化作用。对于所有的药物，一些剂量与咪达唑仑没有相同的区别作用，但有加强作用。最后一次自我注射后测试的概化梯度与第一次自我注射后测试的概化梯度相似。结论：一种药物对同一药理学类训练药物的鉴别作用与其强化作用不具有同构性。
Rationale: If a psychoactive drug shares discriminative effects with one that maintains self-administration, it is often inferred that the test drug is likely to be self-administered and to have abuse liability. This presumed predictive relationship has not been studied directly, however. Objective: To determine at the level of the individual subject (1) whether a novel drug dose that shares discriminative effects with a reinforcing drug dose also will serve as a reinforcer, and (2) whether the results of generalization tests for drugs pharmacologically similar to the training drug predict whether the test drugs will or will not be self-administered. Methods: Baboons were trained to discriminate midazolam (0.32 mg/kg, IV) from saline and also under a schedule of IV drug reinforcement. At the beginning of a period of self-administration, the first self-injection was followed 10 min later by a drug discrimination test session. The baboon then had the opportunity to self-administer the same dose 24 h/day (3-h timeout after each injection). A second drug discrimination test followed the last self-injection of the condition. Results: Zolpidem and imidazenil shared discriminative effects with midazolam. Zolpidem was reinforcing in all baboons, but imidazenil was not. Chlordiazepoxide partially shared discriminative effects with midazolam, and the rate of self-administration was low. Pentobarbital did not share discriminative effects with midazolam, but was reinforcing. For all drugs, some doses did not share discriminative effects with midazolam but were reinforcing. Generalization gradients from tests after the last self-injection were similar to those after the first self-injection. Conclusions: The discriminative effect of a drug in relation to a training drug of the same pharmacological class is not isomorphic with its reinforcing effectiveness.