Gauvin D.V., Holloway F.A.
University of Oklahoma Health Sciences Center, Department of Psychiatry and Behavioral Sciences, Research Building, 306-R, P.O. Box 26901, Oklahoma City, OK 73190-3000, USA.
Behav Pharmacol. 1991 Nov;2(4 And 5):417-428.
Sprague-Dawley rats were trained in a three-choice drug discrimination task utilizing 5mg/kg chlordiazepoxide (CDP), saline (SAL), and 15mg/kg pentylenetetrazole (PTZ) as stimulus conditions. Generalization tests of the three training conditions resulted in exclusively injection-appropriate lever selection. Cross-generalization tests with PTZ or CDP resulted in dose-dependent lever selections confined to the training drug and SAL levers. Morphine and ethanol cross-generalization tests produced saline-appropriate responding, whereas cocaine and caffeine produced PTZ-appropriate responding at high doses. Tests conducted after concomitant administration of both training drugs demonstrated a reciprocal antagonism between the two drugs. More importantly, when the training dose of CDP was held constant and combined with increasing doses of PTZ, a shift from CDP- to PTZ-appropriate responding through a dose range of exclusive SAL-appropriate responding was demonstrated. Overt behavioral indices of seizure activity occurred at dose combinations that engendered only saline responding, but PTZ-appropriate responding did not correspond with the development of overt seizure episodes. These data suggest that the PTZ discriminative cue in the present three-choice paradigm is not primarily linked to its proconvulsant effects. The data are discussed in terms of an hypothesis in which the discriminable interoceptive cues for PTZ and CDP lie at opposite ends of a single continuum that has a neutral centroid, and this continuum more likely reflects an anxiolysis-anxiogenesis dimension than an anticonvulsant-seizure dimension.
将Sprague-Dawley大鼠训练至可在三选择药物辨别任务中，使用5mg/kg氯氮卓（CDP）、生理盐水（SAL）和15mg/kg戊四氮（PTZ）作为刺激条件。对这三种训练条件进行的泛化测试结果显示，大鼠仅选择与注射药物相对应的杠杆。用PTZ或CDP进行的交叉泛化测试结果显示，杠杆选择呈剂量依赖性，且仅限于训练药物和生理盐水对应的杠杆。吗啡和乙醇的交叉泛化测试产生了与生理盐水对应的反应，而可卡因和咖啡因在高剂量时产生了与PTZ对应的反应。同时给予两种训练药物后进行的测试表明，两种药物之间存在相互拮抗作用。更重要的是，当CDP的训练剂量保持不变并与递增剂量的PTZ联合使用时，结果显示在仅与生理盐水对应的反应剂量范围内，出现了从与CDP对应的反应向与PTZ对应的反应的转变。在仅产生与生理盐水对应的反应的剂量组合下出现了癫痫发作活动的明显行为指标，但与PTZ对应的反应与明显癫痫发作事件的发生并不对应。这些数据表明，在当前的三选择范式中，PTZ的辨别线索并非主要与其促惊厥作用相关。这些数据是根据一个假设进行讨论的，即PTZ和CDP的可辨别内感受性线索位于一个单一连续体的两端，该连续体的中心为中性，并且这个连续体更可能反映的是抗焦虑 - 致焦虑维度，而非抗惊厥 - 癫痫维度。
