Schulze G E, Gillam M P, Paule M G
Department of Toxicology, Bristol-Myers Squibb Company, Evansville, IN 47721.
Life Sci. 1992;51(7):487-97. doi: 10.1016/0024-3205(92)90025-k.
The acute behavioral effects of atropine sulfate were assessed using a battery of complex food-reinforced operant tasks that included: temporal response differentiation (TRD, n = 7); delayed matching-to-sample (DMTS, n = 6), progressive ratio (PR, n = 8), incremental repeated acquisition (IRA, n = 8), and conditioned position responding (CPR, n = 8). Performance in these tasks is thought to depend primarily upon specific brain functions such as time perception, short-term memory and attention, motivation, learning, and color and position discrimination, respectively. Atropine sulfate (0.01-0.56 mg/kg iv), given 15-min pretesting, produced significant dose-dependent decreases in the number of reinforcers obtained in all tasks. Response rates decreased significantly at greater than or equal to 0.03 mg/kg for the learning and discrimination tasks, at greater than or equal to 0.10 mg/kg for the motivation and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Response accuracies were significantly decreased at doses greater than or equal to 0.10 mg/kg for the learning, discrimination, and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Thus, the order of task sensitivity to any disruption by atropine is learning = color and position discrimination greater than time perception = short-term memory and attention = motivation (IRA = CPR greater than TRD = DMTS = PR). Thus in monkeys, the rates of responding in operant tasks designed to model learning and color and position discrimination were the most sensitive measures to atropine's behavioral effects. Accuracy in these same task was also disrupted but at higher doses. These data support the hypothesis that cholinergic systems play a greater role in the speed (but not accuracy) of performance of our learning and discrimination tasks compared to all other tasks. Accuracy of responding in these and the short-term memory task, all of which involve the use of lights as visual stimuli, was more sensitive to disruption by atropine than those tasks which did not utilize such strong visual stimuli.
使用一系列复杂的食物强化操作性任务评估硫酸阿托品的急性行为效应，这些任务包括：时间反应辨别（TRD，n = 7）；延迟匹配样本（DMTS，n = 6）、渐进比率（PR，n = 8）、增量重复习得（IRA，n = 8）和条件位置反应（CPR，n = 8）。这些任务中的表现被认为主要分别取决于特定的脑功能，如时间感知、短期记忆和注意力、动机、学习以及颜色和位置辨别。在预测试前15分钟静脉注射硫酸阿托品（0.01 - 0.56 mg/kg），导致所有任务中获得的强化物数量出现显著的剂量依赖性减少。对于学习和辨别任务，当剂量大于或等于0.03 mg/kg时反应率显著下降；对于动机、短期记忆和注意力任务，当剂量大于或等于0.10 mg/kg时反应率显著下降；对于时间感知任务，当剂量大于或等于0.30 mg/kg时反应率显著下降。对于学习、辨别、短期记忆和注意力任务，当剂量大于或等于0.10 mg/kg时反应准确性显著下降；对于时间感知任务，当剂量大于或等于0.30 mg/kg时反应准确性显著下降。因此，对阿托品干扰的任务敏感性顺序为：学习 = 颜色和位置辨别大于时间感知 = 短期记忆和注意力 = 动机（IRA = CPR大于TRD = DMTS = PR）。因此在猴子中，旨在模拟学习以及颜色和位置辨别的操作性任务中的反应率是对阿托品行为效应最敏感的指标。这些相同任务中的准确性也受到干扰，但所需剂量更高。这些数据支持以下假设：与所有其他任务相比，胆碱能系统在我们的学习和辨别任务的执行速度（而非准确性）中发挥更大作用。这些任务以及短期记忆任务中的反应准确性，所有这些任务都使用灯光作为视觉刺激，比那些未使用此类强烈视觉刺激的任务对阿托品干扰更敏感。
