ACUTE BEHAVIORAL-EFFECTS OF MK-801 IN RHESUS-MONKEYS - ASSESSMENT USING AN OPERANT TEST BATTERY
ACUTE BEHAVIORAL-EFFECTS OF MK-801 IN RHESUS-MONKEYS - ASSESSMENT USING AN OPERANT TEST BATTERY
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DOI：
10.1016/0091-3057(94)90203-8
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发表时间：
1994-08-01
影响因子：
3.6
通讯作者：
PAULE, MG
中科院分区：
文献类型：
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作者：
BUFFALO, EA;GILLAM, MP;PAULE, MG
MK-801是一种选择性的非竞争性NMDA受体拮抗剂，使用复杂食物强化任务的操作性测试组合（OTB）评估MK-801的急性效应，这些任务被认为取决于相对特定的大脑功能，如为食物而工作的动机（累进比，PR），学习（增量重复采集，伊拉），颜色和位置识别（条件位置反应，CPR），时间估计（时间反应分化，TRD），以及短期记忆和注意力（延迟匹配样本，DMTS）。终点包括应答率（RR）、准确性（ACC）和任务完成百分比（PTC）。MK-801（0.003-0.075 mg/kg，IV）在试验前15分钟给药，在剂量大于或等于0.03 mg/kg时，伊拉和TRD性能指标出现显著剂量依赖性降低。在这两项任务中，MK-801在剂量低于影响反应率所需剂量时，准确度显著降低。MK-801还导致PR、CPR和DMTS指标出现统计学显著性降低，但仅在较高剂量（大于或等于0.056 mg/kg）时，才导致应答率和准确度显著降低。这些结果表明，在猴子中，设计用于模拟学习和时间估计的操作性任务的表现比模拟动机、颜色和位置辨别以及短期记忆和注意力的任务的表现对MK-801的破坏性影响更敏感。
The acute effects of MK-801, a selective, noncompetitive NMDA receptor antagonist, were assessed using an operant test battery (OTB) of complex food-reinforced tasks that are thought to depend upon relatively specific brain functions such as motivation to work for food (progressive ratio, PR), learning (incremental repeated acquisition, IRA), color and position discrimination (conditioned position responding, CPR), time estimation (temporal response differentiation, TRD), and short-term memory and attention (delayed matching-to-sample, DMTS). Endpoints included response rates (RR), accuracies (ACC), and percent task completed (PTC). MK-801 (0.003-0.075 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent decreases in measures of IRA and TRD performance at doses greater than or equal to 0.03 mg/kg. In both tasks, MK-801 produced significant decreases in accuracy at doses lower than those required to affect response rate. MK-801 also produced statistically significant decreases in PR, CPR, and DMTS measures, but only at higher doses (greater than or equal to 0.056 mg/kg) that caused significant decreases in both response rates and accuracies. These results indicate that, in monkeys, performance of operant tasks designed to model learning and time estimation is more sensitive to the disruptive effects of MK-801 than performance of tasks that model motivation, color, and position discrimination, and short-term memory and attention.