Baron S.P., Butelman E.R., Woods J.H.
Department of Psychology, University of Michigan Medical School, M6322 Medical Science Building I, Ann Arbor, MI 48109-0626, USA.
Behav Pharmacol. 1993 Apr;4(2):115-123.
White Carneaux pigeons (Columbo livia) and rhesus monkeys (Macaca mulatta) were trained to discriminate NMDA from saline in a two-response operant procedure. Both species dose dependently generalized NMDA to the training stimulus, although training was difficult and stimulus control was difficult to maintain. The competitive antagonist CGS 19755 (0.32 and 1.0mg/kg) blocked the discriminative stimulus produced by the training dose of NMDA in pigeons and monkeys. The same doses of CGS 19755 produced rightward, but not dose-dependent, shifts in the NMDA dose-response function in pigeons The non-competitive NMDA antagonist PCP was unable to block the discriminative stimulus produced by the training dose of NMDA in pigeons. Kainate and AMPA, as well as morphine, pentobarbital and d-amphetamine, engendered >/= 90% NMDA-appropriate responding in at least 50% of pigeons tested. The finding that compounds form several different classes generalize to the training dose of NMDA suggests that the present discrimination lacks pharmacological selectivity. This discrimination may not serve efficiently as a procedure in which to examine NMDA agonist and/or antagonist activity.
在两反应操作性程序中，训练白卡诺鸽（Columbo livia）和恒河猴（Macaca mulatta）区分N-甲基-D-天冬氨酸（NMDA）和生理盐水。尽管训练困难且刺激控制难以维持，但两个物种都对训练刺激产生了剂量依赖性的NMDA泛化。竞争性拮抗剂CGS 19755（0.32和1.0mg/kg）阻断了训练剂量的NMDA在鸽和猴中产生的辨别刺激。相同剂量的CGS 19755使鸽的NMDA剂量反应函数向右移动，但不具有剂量依赖性。非竞争性NMDA拮抗剂苯环己哌啶无法阻断训练剂量的NMDA在鸽中产生的辨别刺激。在至少50%接受测试的鸽中，海人酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸，以及吗啡、戊巴比妥和右旋苯丙胺产生了≥90%的NMDA适应性反应。多种不同类别的化合物对训练剂量的NMDA产生泛化，这一发现表明当前的辨别缺乏药理学选择性。这种辨别可能无法有效地作为一种检测NMDA激动剂和/或拮抗剂活性的程序。
