Frederick D L, Gillam M P, Allen R R, Paule M G
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079-9502, USA.
Pharmacol Biochem Behav. 1995 Dec;52(4):789-97. doi: 10.1016/0091-3057(95)00182-v.
The effects of phencyclidine (PCP; a noncompetitive NMDA antagonist) were assessed in rhesus monkeys using performance in an operant test battery (OTB) consisting of five food-reinforced tasks thought to engender responses dependent upon aspects of time estimation, short-term memory, motivation, learning, and color and position discrimination. End-points included percent task completed (PTC), response rate or latency, and response accuracy. Testing occurred 15 min after IV injections of PCP (0.00, 0.003, 0.01, 0.03, 0.1, 0.13, 0.18, and 0.3 mg/kg). PCP disrupted performance of all tasks at 0.30 mg/kg. PTC was significantly decreased in the time estimation, motivation, and learning tasks at doses > or = 0.13 mg/kg. PTC for the short-term memory and color and position discrimination tasks was significantly decreased at 0.18 mg/kg and above. Response rate was significantly decreased at 0.13 mg/kg and above in the motivation and learning tasks and at 0.18 mg/kg and above in the time estimation, short-term memory, and color and position discrimination tasks. Response accuracy was significantly decreased in the time estimation, short-term memory, and learning tasks at doses > or = 0.13 mg/kg, while accuracy in the color and position discrimination task was decreased only at 0.30 mg/kg. PCP's effects on OTB performance were generally nonspecific, in that the time estimation, short-term memory, learning, and motivation tasks were all equally sensitive, with the color and position discrimination task being the least sensitive. These results are different than those obtained from earlier studies on the effects of MK-801, a more selective noncompetitive NMDA antagonist.
使用由五项食物强化任务组成的操作性测试组(OTB)来评估恒河猴中苯环利定(PCP;一种非竞争性NMDA拮抗剂)的作用,这些任务被认为会引发依赖于时间估计、短期记忆、动机、学习以及颜色和位置辨别等方面的反应。终点指标包括完成任务的百分比(PTC)、反应率或潜伏期以及反应准确性。在静脉注射PCP(0.00、0.003、0.01、0.03、0.1、0.13、0.18和0.3mg/kg)15分钟后进行测试。PCP在0.30mg/kg时扰乱了所有任务的表现。在剂量≥0.13mg/kg时,时间估计、动机和学习任务中的PTC显著降低。短期记忆以及颜色和位置辨别任务的PTC在0.18mg/kg及以上时显著降低。在动机和学习任务中,0.13mg/kg及以上时反应率显著降低;在时间估计、短期记忆以及颜色和位置辨别任务中,0.18mg/kg及以上时反应率显著降低。在剂量≥0.13mg/kg时,时间估计、短期记忆和学习任务中的反应准确性显著降低,而颜色和位置辨别任务中的准确性仅在0.30mg/kg时降低。PCP对OTB表现的影响通常是非特异性的,因为时间估计、短期记忆、学习和动机任务都同样敏感,颜色和位置辨别任务最不敏感。这些结果与早期关于更具选择性的非竞争性NMDA拮抗剂MK-801作用的研究结果不同。