Xie Z C, Buckner E, Commissaris R L
Department of Pharmaceutical Sciences, College of Pharmacy and AHP, Wayne State University, Detroit, MI 48202, USA.
Pharmacol Biochem Behav. 1995 Aug;51(4):635-40. doi: 10.1016/0091-3057(94)00428-l.
The present study examined the time course and chronic treatment effects of the noncompetitive N-methyl-D aspartate (NMDA) antagonist, MK-801 (dizocilpine), on conflict behavior in the conditioned suppression of drinking (CSD) paradigm, a repeated-measures conflict task. In daily 10-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 responding and unpunished responding. In the first experiment, the effects of MK-801 administered IP were determined in female and male rats following a range of pretreatment intervals (i.e., 0.5-48 h). In female rats, 0.2 mg/kg MK-801 exerted an anticonflict effect at pretreatment intervals of 10-36 h, but not before 10 h or after 36 h. In male rats, qualitatively similar results were obtained; MK-801 (0.4 mg/kg) exerted anticonflict effects following pretreatment intervals of 6-14 h, but not before 6 or after 14 h. In the second experiment, chronic treatment of female rats with 0.04, 0.01, or 0.2 mg/kg MK-801 resulted in a dose-dependent anticonflict effect in CSD paradigm, which remained stable over the course of 5 weeks of chronic treatment. Punished responding returned to pretreatment levels within 2-3 days after discontinuation of chronic treatment with MK-801. These data suggest that MK-801 exerts a delayed anticonflict effect in both female and male rats with a qualitatively similar pattern, and that there is no tolerance to the anticonflict effect of MK-801 with chronic treatment.
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）范式中冲突行为的时程和慢性治疗效果，CSD范式是一种重复测量冲突任务。在每天10分钟的实验环节中，限水大鼠从一根偶尔会通电的管子饮水（由音调信号提示0.25毫安或0.5毫安电击）。经过训练的实验对象（4周CSD测试）在受惩罚反应和未受惩罚反应方面均表现出稳定的基线。在第一个实验中，在一系列预处理间隔时间（即0.5 - 48小时）后，测定腹腔注射MK-801对雌性和雄性大鼠的影响。在雌性大鼠中，0.2毫克/千克的MK-801在预处理间隔时间为10 - 36小时时发挥抗冲突作用，但在10小时之前或36小时之后则无此作用。在雄性大鼠中，获得了定性相似的结果；MK-801（0.4毫克/千克）在预处理间隔时间为6 - 14小时时发挥抗冲突作用，但在6小时之前或14小时之后则无此作用。在第二个实验中，用0.04、0.01或0.2毫克/千克的MK-801对雌性大鼠进行慢性治疗，在CSD范式中产生了剂量依赖性抗冲突作用，在5周的慢性治疗过程中保持稳定。在用MK-801进行慢性治疗停药后2 - 3天内，受惩罚反应恢复到预处理水平。这些数据表明，MK-801在雌性和雄性大鼠中均发挥延迟抗冲突作用，模式定性相似，并且慢性治疗对MK-801的抗冲突作用不存在耐受性。
