NMDA受体拮抗剂氯胺酮对苯丙胺类中枢兴奋剂条件性位置偏爱效应的影响

目的研究单独使用甲基苯丙胺(methamphetamine,MA)或氯胺酮及两者联合给药致小鼠条件性位置偏爱(conditioned place preference,CPP)效应及停药后和停药后重激发的位置偏爱的变化情况。方法36只♂昆明小鼠分为4组,分别为生理盐水对照组(10ml·kg-1,ip)、MA给药组(2mg·kg-1,ip)、氯胺酮给药组(15mg·kg-1,ip)、MA与氯胺酮合用组(MA2mg·kg-1,ip;氯胺酮15mg·kg-1,ip,提前30min注射)。采用倾向性训练程序训练小鼠,训练8d,隔天进行药物匹配训练,隔天生理盐水训练。停药24d后,氯胺酮组和两药合用组位置偏爱消失后,d25采用训练期时所用药物一半的剂量进行激发。分别记录15min之内小鼠各阶段在伴药侧停留的时间。结果MA或氯胺酮单独使用以及两者联合给药均可使小鼠出现CPP。氯胺酮的CPP效应维持时间较短,停药d9已消失,同时可抑制MA的CPP持续时间,两组再次激发均不重现。MA组小鼠位置偏爱在停药后25d里并未消失,激发后可使该效应显著增强。结论氯胺酮也是一种能够促使小鼠产生位置偏爱的药物,停药后短期内可增强MA引起位置偏爱的强度,但可抑制CPP的维持时间,同时抑制MA再激发后CPP重现。

EFFECTS OF THE NON - COMPETITIVE NMDA RECEPTOR ANTAGONIST KETAMINE ON AMPHETAMINE TYPE STIMULANTS INDUCED PLACE PREFERENCE IN MICE

Objective:To investigate the conditioned place preference (CPP) and sensitization induced by methamphetamine (MA) or ketamine,a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist in mice,and the effect of ketamine on MA-induced CPP and sensitization. Methods:Thirty-six male Kunming mice were divided into 4 groups, and treated with normal saline (10 ml·kg -1 ,ip), MA (2 mg·kg -1 ,ip), ketamine (15 mg·kg -1 ,ip),and ketamine (15 mg·kg -1 ,ip, 30 min before MA) combined with MA(2 mg·kg -1 ,ip), respectively. Place conditioning was conducted according to a biased procedure for 8 days. After drug withdrawal for 24 days, CPP in ketamine group and the combination group disappeared, and then on d2 MA or ketamine in half dose was administrated again for sensitization study. The time spent in the experimental compartment during a 15-min session of each mouse was measured in every stage. Results:MA (2 mg·kg -1 ,ip) produced a long-lasting CPP in mice. Ketamine (15 mg·kg -1 ,ip) also produced a preference for the drug-associated place, which disappeared in 9 days after drug withdrawal. Pretreatment with ketamine (15 mg·kg -1 ,ip) suppressed the maintenance of CPP produced by MA. After the disappearance of CPP in the combination group,no mice showed place preference after the challenge of 1 mg·kg -1 MA combined with 7.5 mg·kg -1 ketamine. The mice treated with MA alone maintained CPP for 25 days after drug withdrawal and showed more significant place preference with a challenge of 1 mg·kg -1 MA. Conclusion: Ketamine is a kind of drug which can also produce CPP in mice. But it can suppress the maintenance of CPP produced by MA and the priming of MA.