Mobini S, Chiang T J, Ho M Y, Bradshaw C M, Szabadi E
Division of Psychiatry, University of Nottingham, Medical School, Queen's Medical Centre, UK.
Psychopharmacology (Berl). 2000 Sep;152(1):47-54. doi: 10.1007/s002130000486.
Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on "reinforcer efficacy". It has been proposed that the effects of neuroleptic drugs on operant behaviour are mediated by a reduction of "reinforcer efficacy". We examined the effects of two "conventional" neuroleptics (haloperidol and chlorpromazine) and an "atypical" neuroleptic (clozapine) on progressive ratio schedule performance; d-amphetamine was used as a comparison compound. In experiment 1, rats responded for a sucrose reinforcer on a time-constrained progressive ratio schedule (75-min sessions). After 66 preliminary training sessions, the rats received single doses (IP) of haloperidol (0.05, 0.1 mg kg(-1)). chlorpromazine (2, 4 mg kg(-1)), clozapine (0.5, 1, 2, 4, 8 mg kg(-1)), and d-amphetamine (0.2, 0.4, 0.8 mg kg(-1)), and the corresponding vehicle solutions. The highest ratio completed was reduced by haloperidol and chlorpromazine, and increased by clozapine. All three neuroleptics reduced the peak response rate, at least at the highest doses administered. Response rates on the lower and intermediate ratios could be described by a three-parameter equation proposed to account for fixed ratio schedule performance. Haloperidol reduced, and clozapine dose-dependently increased the "motivational" parameter (a); d-amphetamine reduced it at low doses and increased it at high doses. The three neuroleptics increased the "response time" parameter (delta). Un-reinforced locomotor behaviour, measured in experiment 2, was not significantly altered by haloperidol, chlorpromazine or clozapine, but was increased by d-amphetamine. These results are consistent with a reduction of reinforcer efficacy produced by haloperidol and an increase produced by clozapine; clozapine's effect is unlikely to reflect a general increase in locomotion. All three neuroleptics induced some degree of motor debilitation. The quantitative analysis of progressive ratio schedule performance may provide a useful adjunct to existing methods for separating effects of drugs on motivational and motor processes.
渐进比率时间表上的表现已被提议作为评估药物对“强化物效能”影响的一种方法。有人提出，抗精神病药物对操作性行为的影响是通过降低“强化物效能”来介导的。我们研究了两种“传统”抗精神病药物（氟哌啶醇和氯丙嗪）和一种“非典型”抗精神病药物（氯氮平）对渐进比率时间表表现的影响；右旋苯丙胺用作对照化合物。在实验1中，大鼠在时间受限的渐进比率时间表（75分钟时段）上对蔗糖强化物做出反应。经过66次初步训练后，大鼠接受单次腹腔注射剂量的氟哌啶醇（0.05、0.1毫克/千克）、氯丙嗪（2、4毫克/千克）、氯氮平（0.5、1、2、4、8毫克/千克）和右旋苯丙胺（0.2、0.4、0.8毫克/千克），以及相应的溶剂溶液。氟哌啶醇和氯丙嗪降低了完成的最高比率，而氯氮平则提高了该比率。所有三种抗精神病药物至少在给予的最高剂量下降低了峰值反应率。较低和中等比率的反应率可以用一个为解释固定比率时间表表现而提出的三参数方程来描述。氟哌啶醇降低了，氯氮平剂量依赖性地增加了“动机”参数（a）；右旋苯丙胺在低剂量时降低了它，在高剂量时增加了它。这三种抗精神病药物增加了“反应时间”参数（δ）。在实验2中测量的无强化运动行为，未被氟哌啶醇、氯丙嗪或氯氮平显著改变，但被右旋苯丙胺增加。这些结果与氟哌啶醇导致强化物效能降低以及氯氮平导致强化物效能增加一致；氯氮平的作用不太可能反映运动的普遍增加。所有三种抗精神病药物都引起了一定程度的运动能力下降。对渐进比率时间表表现的定量分析可能为现有的区分药物对动机和运动过程影响的方法提供有用的辅助。
