Domino K B, Domino E F
Arch Int Pharmacodyn Ther. 1976 Dec;224(2):248-57.
The effects of scopolamine HBr (0.032 to 10.0 mg/kg), methscopolamine Br (1.0 and 10.0 mg/kg) and 0.36 mg/kg NaBr on acquisition and retention of one-way avoidance behavior and total brain acetylcholine (ACh) were studied in male albino rats. Compared to equimolar NaBr, scopolamine caused a dose-related impairment in acquisition of avoidance responding while methscopolamine did not. Retention of avoidance behavior in trained rats was also disrupted, but the detrimental effect was smaller and occurred only following large doses of scopolamine. The per cent escape behavior was not decreased by any of the treatments. It increased as avoidance was decreased. Scopolamine caused a dose-related increase in latency and avoidance and escape responding compared to equimolar NaBr. However, scopolamine increased the latency of avoidance at lower doses and to a greater degree than it increased the latency of escape. Escape latencies were significantly increased only at the largest dose (10 mg/kg). These dose-related effects of scopolamine were greater during acquisition than during retention. Small doses (0.032 mg/kg) shortened latency of avoidance during retention. Methscopolamine increased avoidance and escape latencies only at the largest dose (10 mg/kg). Scopolamine produced a dose-related decrease in brain ACh which correlated well with the per cent avoidance in acquisition (r = 0.95) and retention (r = 0.88) trials. It is concluded that a muscarinic cholinergic antagonist with central actions like scopolamine affects selective aspects of avoidance behavior in low doses, and that these changes are highly correlated with brain ACh levels.
研究了氢溴酸东莨菪碱（0.032至10.0毫克/千克）、溴甲东莨菪碱（1.0和10.0毫克/千克）以及0.36毫克/千克溴化钠对雄性白化大鼠单向回避行为的习得和保持以及全脑乙酰胆碱（ACh）的影响。与等摩尔的溴化钠相比，东莨菪碱对回避反应的习得产生剂量相关的损害，而溴甲东莨菪碱则没有。训练大鼠的回避行为保持也受到干扰，但有害作用较小，且仅在大剂量东莨菪碱作用后出现。任何一种处理均未降低逃避行为的百分比。随着回避行为减少，其增加。与等摩尔的溴化钠相比，东莨菪碱使潜伏期、回避和逃避反应呈剂量相关增加。然而，东莨菪碱在较低剂量时增加回避潜伏期的程度大于增加逃避潜伏期的程度。仅在最大剂量（10毫克/千克）时逃避潜伏期显著增加。东莨菪碱的这些剂量相关作用在习得过程中比在保持过程中更大。小剂量（0.032毫克/千克）在保持过程中缩短回避潜伏期。溴甲东莨菪碱仅在最大剂量（10毫克/千克）时增加回避和逃避潜伏期。东莨菪碱使脑ACh呈剂量相关减少，这与习得（r = 0.95）和保持（r = 0.88）试验中的回避百分比密切相关。结论是，具有中枢作用的毒蕈碱胆碱能拮抗剂如东莨菪碱在低剂量时影响回避行为的选择性方面，且这些变化与脑ACh水平高度相关。
