Grant K.A., Knisely J.S., Tabakoff B., Barrett J.E., Balster R.L.
Unit for Special Projects, National Institute of Alcohol Abuse and Alcoholism.
Behav Pharmacol. 1991 Apr;2(2):87-95.
The discriminative stimulus effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists were investigated in animals trained to discriminate 1.5g/kg (pigeons) or 1.25g/kg (mice) ethanol from vehicle. Key-pecking of pigeons and lever responding of mice were maintained under fixed ratio schedules of mixed grain or milk reinforcement, respectively. Phencyclidine (PCP) and ketamine dose-dependently substituted for the ethanol stimulus in both species, with PCP being about 10-fold more potent than ketamine. In pigeons, PCP and ketamine fully substituted for ethanol at doses that did not significantly alter rates of responding; with mice, complete substitution was accompanied by response rate-decreasing effects. In pigeons, the highly selective NMDA receptor/ionophore antagonist MK-801 also substituted for ethanol at a dose that was accompanied by reduced response rates. Compounds that did not substitute for the ethanol stimulus were cocaine (both species), the 5-HT(1B) receptor agonist TFMPP (pigeon), the H(1) receptor antagonist hydroxyzine (mice), and the anticonconvulsants phenytoin and ethosuximide (mice). The present data show that PCP-like drugs that are antagonists of NMDA receptor-mediated neurotransmission share common discriminative stimulus effects with ethanol.
在训练以区分1.5g/kg（鸽子）或1.25g/kg（小鼠）乙醇与溶剂的动物中，研究了非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂的辨别性刺激作用。鸽子的啄键行为和小鼠的杠杆反应分别在混合谷物或牛奶强化的固定比率时间表下维持。苯环己哌啶（PCP）和氯胺酮在两个物种中均呈剂量依赖性地替代乙醇刺激，PCP的效力比氯胺酮高约10倍。在鸽子中，PCP和氯胺酮在不显著改变反应率的剂量下完全替代乙醇；在小鼠中，完全替代伴随着反应率降低的效应。在鸽子中，高选择性NMDA受体/离子载体拮抗剂MK-801也在伴随着反应率降低的剂量下替代乙醇。不能替代乙醇刺激的化合物有可卡因（两个物种）、5-HT(1B)受体激动剂TFMPP（鸽子）、H(1)受体拮抗剂羟嗪（小鼠）以及抗惊厥药苯妥英和乙琥胺（小鼠）。目前的数据表明，作为NMDA受体介导的神经传递拮抗剂的类PCP药物与乙醇具有共同的辨别性刺激作用。
