van Haaren F, van Hest A, van Hattum T
Netherlands Institute for Brain Research, Amsterdam.
Pharmacol Biochem Behav. 1989 Jun;33(2):361-5. doi: 10.1016/0091-3057(89)90514-5.
Male and female Wistar rats were trained on a fixed-consecutive-number schedule in which a response on a food lever was followed by the presentation of reinforcement when at least three, but not more than seven responses had been completed on a work lever. Subjects were treated with different doses of the centrally acting cholinergic antagonist scopolamine hydrobromide or the more peripherally active cholinergic antagonist scopolamine methylbromide (0.08, 0.16 or 0.32 mg/ml/kg) once behavior had stabilized. Scopolamine hydrobromide and scopolamine methylbromide dose-dependently decreased response rates in males and females. Scopolamine methylbromide decreased response rates more than equivalent doses of scopolamine hydrobromide and the rate-suppressant effects of both drugs were more marked in males than in females. Scopolamine hydrobromide dose-dependently decreased response accuracy, but differences between males and females were not observed. Response accuracy also decreased after scopolamine methylbromide, but did not vary as a function of the dose of the drug. The decrease in response accuracy induced by both drugs was attributable to an increase in the percentage of trials with a premature switch from the work lever to the food lever. Both scopolamine hydrobromide and scopolamine methylbromide dose-dependently increased the number of premature switches. Differences between males and females were not observed. Administration of scopolamine hydrobromide and scopolamine methylbromide also decreased the number of obtained reinforcers in a dose-dependent manner. Females obtained significantly fewer reinforcers than males, while scopolamine methylbromide affected the number of obtained reinforcers to a larger extent than scopolamine hydrobromide.
对雄性和雌性Wistar大鼠进行固定连续数强化程序训练,即当在工作杆上完成至少3次但不超过7次反应后,按压食物杆会得到强化物。当行为稳定后,用不同剂量的中枢作用胆碱能拮抗剂氢溴酸东莨菪碱或外周作用更强的胆碱能拮抗剂甲溴东莨菪碱(0.08、0.16或0.32毫克/毫升/千克)对实验对象进行处理。氢溴酸东莨菪碱和甲溴东莨菪碱剂量依赖性地降低了雄性和雌性大鼠的反应率。甲溴东莨菪碱比同等剂量的氢溴酸东莨菪碱更能降低反应率,且两种药物对反应率的抑制作用在雄性大鼠中比在雌性大鼠中更明显。氢溴酸东莨菪碱剂量依赖性地降低了反应准确性,但未观察到雄性和雌性之间的差异。甲溴东莨菪碱处理后反应准确性也降低了,但与药物剂量无关。两种药物引起的反应准确性下降是由于从工作杆过早切换到食物杆的试验百分比增加所致。氢溴酸东莨菪碱和甲溴东莨菪碱均剂量依赖性地增加了过早切换的次数。未观察到雄性和雌性之间的差异。给予氢溴酸东莨菪碱和甲溴东莨菪碱也以剂量依赖性方式减少了获得的强化物数量。雌性获得的强化物明显少于雄性,而甲溴东莨菪碱比氢溴酸东莨菪碱对获得的强化物数量影响更大。