左旋四氢巴马汀对可卡因泛化甲基苯丙胺效应的影响

目的:了解不同剂量的左旋四氢巴马汀(l-THP)对成瘾药物精神依赖性的影响。方法:用固定比强化方法使大鼠对可卡因(10·00mg·kg-1)形成稳定的辨别行为。以不同剂量的l-THP(0·63、1·25、2·50、5·00mg·kg-1)或甲基苯丙胺(MA)(0·03、0·06、0·13、0·25mg·kg-1)替代训练剂量的可卡因;以l-THP拮抗可卡因的泛化效应,并与D1和D2受体拮抗剂SCH23390和雷可必利的效应对照。结果:10·00mg·kg-1剂量的可卡因能使大鼠形成稳定的辨别行为;训练剂量的可卡因不能泛化本实验所使用的任何一种剂量的l-THP,但可泛化0·25mg·kg-1以上剂量的MA。SCH23390、雷可必利和l-THP均可显著减弱可卡因对MA的泛化效应。结论:在本实验系统中,可卡因可使大鼠形成稳定的辨别效应;可卡因能泛化MA;DA受体参与调控这种泛化效应,l-THP能显著降低可卡因泛化MA的效应表明它能降低MA精神依赖性的形成。

EFFECTS OF 1- THP ON COCAINE GENERALIZATION TO METHAMPHETAMINE

Objective: To explore the effects of l-tetrahydropalmatine(l-THP) on drugs with psychic dependence producing potential.Methods:Rats were trained to discriminate cocaine(10.00 mg·kg~ - 1) from saline under fixed-ratio schedule. After discrimination was established, l-THP(0.63?1.25?2.50 and 5.00 mg·kg~ -1)or methamphetamine (MA,0.03?0.06?0.13 and 0.25mg·kg~ -1) at different doses were given to substitute for cocaine of training dose; then,the rats were administered with DA receptor antagonists SCH23390 or raclopride or l-THP prior to the injection of MA at different doses to antagonize the effect. Results:The rats acquired discrimination of cocaine from saline. Any dose of l-THP used failed to substitute for cocaine of training dose,while MA at the dose equal to or higher than 0.25 mg·kg~ -1 did. Such generalization effect was attenuated by SCH23390,raclopride and 5.00 mg ·kg~ -1 l -THP significantly. Conclusion:Rats can steadily discriminate cocaine from saline;cocaine of training dose can generalize MA. DA receptors are involved in this effect. The effect of l-THP on cocaine generalization to MA suggests that l-THP can decrease the psychic dependence of MA.