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Differential properties between TRK-820 and U-50,488H on the discriminative stimulus effects in rats

机译：TRK-820和U-50,488H对大鼠歧视性刺激作用的差异性

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摘要

It has been demonstrated that the newly synthesized K-opioid receptor agonist TRK-820, which has a unique structure that is different from those of other prototypical K-opioid receptor agonists such as U-50,488H, exert some behavioral effects that differ from those induced by U-50,488H. Therefore, the present study was designed to examine the possible difference between the discriminative stimulus effects of TRK-820 and U-50,488H in rats. Substitution tests with several K-opioid receptor agonists were initiated in rats trained to discriminate between TRK-820 (40 mug/kg) or U-50,488H (3.0 mg/kg) and saline. In the cross-substitution tests, U-50,488H substituted for the discriminative stimulus effects of TRK-820, whereas TRK-820 did not substitute completely for those of U-50,488H, indicating that the discriminative stimulus effects of TRK-820 and U-50,488H were somewhat different. In the substitution tests, E-2078, but not R-84760, substituted for the discriminative stimulus effects of both TRK-820 and U-50,488H. KT-90, CI-977 and ICI-199441 each substituted for the discriminative stimulus effects of U-50,488H, but not to those of TRK-820. These results imply that these K-opioid receptor agonists possess U-50,488H-like discriminative stimulus effects. Furthermore, that U-50,488H and the other K-Opioid receptor agonists substituted for the discriminative stimulus effects of U-50,488H, produced aversive effects in rats. These findings suggest the possibility that unlike those of TRK-820, the cue of the discriminative stimulus effects of U-50,488H may be, at least in part, associated with its aversive effects. (C) 2004 Elsevier Inc. All rights reserved.
机译：业已证明，新合成的K阿片受体激动剂TRK-820具有不同于其他原型K阿片受体激动剂（如U-50,488H）的独特结构，其行为效果不同于那些由U-50,488H诱导。因此，本研究旨在检查在大鼠中TRK-820和U-50,488H的歧视性刺激作用之间的可能差异。在经过训练以区分TRK-820（40杯/千克）或U-50,488H（3.0毫克/千克）和盐水的大鼠中，发起了几种K型阿片受体激动剂的替代试验。在交叉替代测试中，U-50,488H替代了TRK-820的歧视性刺激作用，而TRK-820并未完全替代U-50,488H的歧视性刺激作用，表明TRK-820和U的歧视性刺激作用-50,488H有所不同。在替代测试中，E-2078替代了TRK-820和U-50,488H的歧视性刺激效果，但没有用R-84760替代。 KT-90，CI-977和ICI-199441分别替代了U-50,488H的歧视性刺激作用，但没有替代TRK-820。这些结果暗示，这些K-阿片样物质受体激动剂具有U-50,488H样的歧视性刺激作用。此外，U-50,488H和其他K阿片受体激动剂替代了U-50,488H的歧视性刺激作用，在大鼠中产生了厌恶作用。这些发现表明，与TRK-820不同的是，U-50,488H的歧视性刺激作用的提示可能至少部分与其反作用有关。 （C）2004 Elsevier Inc.保留所有权利。

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