Haracz J L, Belanger S A, MacDonall J S, Sircar R
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Life Sci. 1995;57(25):2347-57. doi: 10.1016/0024-3205(95)02229-c.
Behavioral sensitization to cocaine was tested for in rats pretreated with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, or D-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (D-CPPene), a competitive NMDA antagonist. A 5-day regimen of once-daily cocaine (15 mg/kg) injections yielded sensitization to cocaine (15 mg/kg)-induced behavioral activation. Cocaine sensitization was partially prevented by MK-801 (0.25 mg/kg) or D-CPPene (20 mg/kg) pretreatment. These results differ from previous reports that NMDA receptor antagonists completely prevented the development of stimulant sensitization. While raising questions about methodological differences among laboratories studying this issue, our findings suggest that sensitization may involve mechanisms dependent on NMDA-receptor function as well as NMDA receptor-independent mechanisms.
对用MK-801（一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂）或D-3-(2-羧基哌嗪-4-基)-1-丙烯基-1-膦酸（D-CPPene，一种竞争性NMDA拮抗剂）预处理的大鼠进行了可卡因行为致敏性测试。为期5天、每天一次注射可卡因（15毫克/千克）的方案产生了对可卡因（15毫克/千克）诱导的行为激活的致敏作用。MK-801（0.25毫克/千克）或D-CPPene（20毫克/千克）预处理可部分预防可卡因致敏。这些结果与之前关于NMDA受体拮抗剂完全阻止兴奋剂致敏发展的报道不同。虽然这引发了对研究该问题的不同实验室之间方法差异的质疑，但我们的研究结果表明，致敏可能涉及依赖于NMDA受体功能的机制以及不依赖于NMDA受体的机制。
