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Effects of atropine on operant test battery performance in rhesus monkeys
G E Schulze1, M P Gillam, M G Paule
1Department of Toxicology, Bristol-Myers Squibb Company, Evansville, IN 47721.
Abstract:
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.