Bondareva Tatiana, Wesołowska Anna, Dukat Małgorzata, Lee Mase, Young Richard, Glennon Richard A
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Box 980540, Virginia Commonwealth University Richmond, Virginia 23298-0540, United States.
Pharmacol Biochem Behav. 2005 Nov;82(3):531-8. doi: 10.1016/j.pbb.2005.10.008. Epub 2005 Dec 7.
Racemic N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxymethamphetamine, MDMA), a central stimulant and empathogenic agent, and cocaine are drugs of abuse that function as training drugs in drug discrimination studies. In tests of stimulus generalization (substitution), asymmetric generalization occurs between the two agents: a (+/-)MDMA stimulus generalized to cocaine, but a cocaine stimulus did not generalize to (+/-)MDMA. A possible explanation may be found, at least in part, in the stimulus effects of the optical isomers of MDMA. In the present study, groups of male Sprague-Dawley rats were trained to discriminate either S(+)MDMA (training dose=1.5 mg/kg, i.p.; n=10; ED50=0.6 mg/kg) or R(-)MDMA (training dose=1.75 mg/kg, i.p.; n=7; ED50=0.4 mg/kg) from saline vehicle using a VI-15s schedule of reinforcement. Tests of stimulus generalization with cocaine were conducted in each of the two groups. Cocaine only partially substituted for the S(+)MDMA stimulus (maximum=39% drug-appropriate responding), and various doses of cocaine did not enhance the percent drug-appropriate responding produced by a low dose (0.5 mg/kg) of S(+)MDMA. In contrast, the R(-)MDMA stimulus generalized completely to cocaine (ED50=1.3 mg/kg). Taken together with an earlier report that a (+/-)MDMA stimulus generalizes to cocaine, it would seem that the stimulus actions of cocaine might share greater similarity with R(-)MDMA than with S(+)MDMA.
消旋N-甲基-1-(3,4-亚甲二氧基苯基)-2-氨基丙烷（亚甲二氧基甲基苯丙胺，摇头丸）是一种中枢兴奋剂和致幻剂，可卡因是滥用药物，在药物辨别研究中用作训练药物。在刺激泛化（替代）测试中，两种药物之间出现不对称泛化：(±)摇头丸刺激可泛化到可卡因，但可卡因刺激不能泛化到(±)摇头丸。至少部分原因可能在于摇头丸光学异构体的刺激效应。在本研究中，将雄性斯普拉格-道利大鼠分组，使用固定间隔15秒强化程序训练它们区分S(+)摇头丸（训练剂量=1.5毫克/千克，腹腔注射；n=10；半数有效剂量=0.6毫克/千克）或R(-)摇头丸（训练剂量=1.75毫克/千克，腹腔注射；n=7；半数有效剂量=0.4毫克/千克）与生理盐水。对两组大鼠都进行了可卡因刺激泛化测试。可卡因仅部分替代S(+)摇头丸刺激（最大替代率=39%的药物相关反应），不同剂量的可卡因均未增强低剂量（0.5毫克/千克）S(+)摇头丸产生的药物相关反应百分比。相比之下，R(-)摇头丸刺激完全泛化到可卡因（半数有效剂量=1.3毫克/千克）。结合早期一份关于(±)摇头丸刺激可泛化到可卡因的报告来看，可卡因的刺激作用似乎与R(-)摇头丸的相似性大于与S(+)摇头丸的相似性。
