Central stimulants as discriminative stimuli:: Asymmetric generalization between (-)ephedrine and S(+)methamphetamine
Central stimulants as discriminative stimuli:: Asymmetric generalization between (-)ephedrine and S(+)methamphetamine
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DOI：
10.1016/s0091-3057(02)00963-2
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发表时间：
2002-12-01
影响因子：
3.6
通讯作者：
Glennon, RA
中科院分区：
文献类型：
--
作者：
Bondareva, TS;Young, R;Glennon, RA
在药物辨别研究中，中枢兴奋剂很容易用作训练刺激，并且通常在刺激泛化测试中相互替代，而不管哪种用作训练药物。我们以前发现，虽然（+）苯丙胺和（-）麻黄碱之间发生了替代，但在对（-）麻黄碱训练的动物给予S（+）甲基苯丙胺后，并没有发生替代。在本研究中，训练大鼠区分S（+）甲基苯丙胺（1 mg/kg）和生理盐水溶剂，并用几种兴奋剂（包括（-）麻黄碱）进行刺激泛化测试。S（+）甲基苯丙胺刺激（ED 50 = 0.06 mg/kg），一般为R（-）甲基苯丙胺（ED 50 = 1.61 mg/kg），S（+）苯丙胺（ED 50 = 0.28 mg/kg），S（-）甲卡西酮（ED 50 = 0.21 mg/kg）、哌甲酯（ED 50 = 0.28 mg/kg）、可卡因（ED 50 = 3.68 mg/kg）和（-）麻黄碱（ED 50 = 13.1 mg/kg）。因此，S（+）甲基苯丙胺和（-）麻黄碱之间的刺激泛化显然是不对称的。在一项配套研究中，对接受过辨别（-）麻黄碱（4毫克/千克）训练的大鼠给予R（-）甲基苯丙胺;发生了替代，发现R（-）甲基苯丙胺（ED 50 = 0.92毫克/千克）与（-）麻黄碱（ED 50 = 0.8毫克/千克）的效力几乎相等。虽然所观察到的结果的确切基础尚不清楚，他们讨论的（-）麻黄碱和甲基苯丙胺光学异构体对神经递质的释放和再摄取的不同影响。(C)2002年爱思唯尔科学公司All rights reserved.
Central stimulants readily serve as training stimuli in drug discrimination studies and typically substitute for one another in tests of stimulus generalization regardless of which is used as training drug. We have previously found that, although substitution occurs between (+)amphetamine and (-)ephedrine, substitution did not occur upon administration of S(+)methamphetamine to (-)ephedrine-trained animals. In the present investigation, rats were trained to discriminate S(+)methamphetamine (1 mg/kg) from saline vehicle and tests of stimulus generalization were performed with several stimulants, including ( -)ephedrine. The S(+)methamphetamine stimulus (ED50 = 0.06 mg/kg) generalized to R(-)methamphetamine (ED50 = 1.61 mg/kg), S(+)amphetamine (ED50 = 0.28 mg/kg), S(-)methcathinone (ED50 = 0.21 mg/kg), methylphenidate (ED50 = 0.28 mg/kg), cocaine (ED50 = 3.68 mg/kg) and (-)ephedrine (ED50 = 13.1 mg/kg). Hence, stimulus generalization between S(+)methamphetamine and (-)ephedrine is apparently asymmetrical. In a companion study, R(-)methamphetamine was administered to rats trained to discriminate (-)ephedrine (4 mg/kg); substitution occurred and R(-)methamphetamine (ED50 = 0.92 mg/kg) was found to be nearly equipotent with (-)ephedrine (ED50 = 0.8 mg/kg). Although the exact basis for the observed results are unclear, they are discussed in terms of the different effects of (-)ephedrine and the methamphetamine optical isomers on neurotransmitter release and reuptake. (C) 2002 Elsevier Science Inc. All rights reserved.