Xie Z, Commissaris R L
Department of Pharmaceutical Sciences, College of Pharmacy and AHP, Wayne State University, Detroit, MI 48202.
Pharmacol Biochem Behav. 1992 Oct;43(2):471-7. doi: 10.1016/0091-3057(92)90178-i.
The present study examined the effects of the noncompetitive NMDA antagonist, MK 801 (dizocilpine), on behavior in the conditioned suppression of drinking (CSD) punished drinking paradigm, a repeated-measures conflict task. In daily 10- or 15-min sessions, water-restricted rats drank from a tube that was occasionally electrified (0.25- or 0.5-mA shocks signaled by a tone). Trained subjects (4 weeks of CSD testing) exhibited stable baselines for both punished (approximately 40 or 100 shocks received/session at the 0.5- and 0.25-mA shock intensities, respectively) and unpunished (approximately 15 ml/session water intake at either shock intensity) responding. Over a wide range of doses, (+) MK 801 did not increase punished responding when administered using a 10-min, 4-h, or 48-h pretreatment. However, at a 24-h pretreatment (+) MK 801 (0.04-0.4 mg/kg, IP) produced a dramatic and dose-dependent increase in punished responding. The "inactive" (-) isomer of MK 801 did not produce a significant anxiolytic-like effect in the CSD paradigm at doses up to 2 mg/kg when tested using a 24-h pretreatment. These data suggest that the anticonvulsant agent (+) MK 801 also may exert antianxiety effects in humans.
本研究考察了非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK 801（地佐环平）对条件性饮水抑制（CSD）惩罚性饮水范式中行为的影响，这是一种重复测量的冲突任务。在每天10或15分钟的实验时段中，限水的大鼠通过一根偶尔会通电的管子饮水（0.25毫安或0.5毫安的电击由一个音调信号提示）。经过训练的受试者（4周的CSD测试）在惩罚性（分别在0.5毫安和0.25毫安电击强度下，每次实验时段大约接受40次或100次电击）和非惩罚性（在任一电击强度下，每次实验时段大约摄入15毫升水）反应方面都表现出稳定的基线。在很宽的剂量范围内，（+）MK 801在进行10分钟、4小时或48小时预处理后给药时，并没有增加惩罚性反应。然而，在进行24小时预处理时，（+）MK 801（0.04 - 0.4毫克/千克，腹腔注射）使惩罚性反应产生了显著的、剂量依赖性的增加。当使用24小时预处理进行测试时，MK 801的“无活性”（-）异构体在剂量高达2毫克/千克时，在CSD范式中并未产生显著的抗焦虑样效应。这些数据表明，抗惊厥药（+）MK 801在人类中也可能发挥抗焦虑作用。
