Galbicka G, Elsmore T F, Witkin J M
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Psychopharmacology (Berl). 1989;97(4):448-55. doi: 10.1007/BF00439546.
The present experiments examined whether the rate and type of events maintaining responding help determine physostigmine's behavioral effects. The first two experiments examined the acute and chronic effects of physostigmine, respectively, on lever pressing of rats under variable-interval schedules of food presentation. The third examined the chronic effects of physostigmine on lever pressing under random-interval schedules of shock avoidance. Three different variable intervals (18, 56, and 180 s) and two different random intervals (20 and 60 s) were studied, each associated with a distinctive stimulus. Baseline rates of responding were directly related to the scheduled rate of food delivery or shock avoidance. Acute administration of 0.154-1.233 mumol/kg (0.1-0.8 mg/kg) physostigmine sulfate produced monotonic decreases in overall response rate under all schedules of food presentation. Acute effects (per cent of control response rate) did not differ systematically under the various interval values. Large doses (i.e., 0.4 or 0.8 mg/kg) suppressed the rate of food delivery as well. When initially administered, 0.967 mumol/kg (0.4 mg/kg) physostigmine salicylate also suppressed avoidance response rates and per cent shocks avoided. Tolerance developed to the effects of this dose of physostigmine salicylate on pellet or shock-avoidance frequency more rapidly than to effects on overall response rate. Tolerance to the latter developed only very gradually and could in the case of shock-avoidance response rates be considered partial at best. Tolerance was not affected by the scheduled rate of food or shock presentation. Blood acetylcholinesterase levels showed no recovery during chronic physostigmine. Tolerance is discussed in terms of the reinforcement-loss hypothesis.
本实验研究了维持反应的事件速率和类型是否有助于确定毒扁豆碱的行为效应。前两个实验分别研究了毒扁豆碱对食物呈现可变间隔时间表下大鼠杠杆按压的急性和慢性影响。第三个实验研究了毒扁豆碱对随机间隔时间表下避免电击的杠杆按压的慢性影响。研究了三种不同的可变间隔（18、56和180秒）和两种不同的随机间隔（20和60秒），每种间隔都与一种独特的刺激相关。反应的基线速率与食物递送或避免电击的预定速率直接相关。急性给予0.154 - 1.233 μmol/kg（0.1 - 0.8 mg/kg）硫酸毒扁豆碱会使所有食物呈现时间表下的总体反应速率呈单调下降。在不同的间隔值下，急性效应（对照反应速率的百分比）没有系统性差异。大剂量（即0.4或0.8 mg/kg）也会抑制食物递送速率。最初给予时，0.967 μmol/kg（0.4 mg/kg）水杨酸毒扁豆碱也会抑制回避反应速率和避免电击的百分比。对该剂量水杨酸毒扁豆碱对颗粒或避免电击频率的影响产生耐受性的速度比对总体反应速率的影响更快。对后者的耐受性发展非常缓慢，在避免电击反应速率的情况下，充其量只能认为是部分耐受性。耐受性不受食物或电击呈现预定速率的影响。在慢性给予毒扁豆碱期间，血液乙酰胆碱酯酶水平没有恢复。根据强化丧失假说对耐受性进行了讨论。
