REARING HISTORY AND BEHAVIORAL RESPONSIVENESS TO COCAINE

这项拟议的工作将调查行为方面的影响 不同养殖史对大鼠免疫反应的影响 可卡因，其中反应性是根据 可卡因的辨别性刺激特性和 可卡因增强或干扰精神运动的能力 性能。行为和行为明显不同的大鼠 神经属性的准备将通过将一半的大鼠暴露在 丰富的养育环境(EC代表丰富的条件)和 另一半到贫穷的环境(IC代表孤立或 贫困状况)断奶后60天。的影响 这些截然不同的历史将在两个层面上进行评估 盐水-可卡因辨别任务。对可卡因的反应性 辨别性刺激的数量将由 学习辨别，通过可卡因的剂量可以 成功地作为一种歧视性的刺激，并在最低限度 歧视性行为泛化的剂量。此外 为了比较IC和EC大鼠在可卡因- 生理盐水歧视范式，拟议的工作还将 确定养育历史是否会影响到 大鼠从可卡因训练线索中归纳出其他药物 高滥用倾向(d-苯丙胺、芬太尼、苯环利定、 咪达唑仑和摇头丸(“摇头丸”))。第一被告(SCH23390)及第二被告 (舒必利)多巴胺受体阻滞剂也将接受评估 他们阻断可卡因线索的能力。电子商务和IC的影响 培养对可卡因的精神运动效应的反应性将是 通过进行基于操作符的剂量-反应分析进行评估 在高或低努力的情况下保持业绩 需求。操作力测量方法，它允许 记录每个响应的峰值力量和持续时间 (包括常规检测不到的次标准响应 方法)，将在所有拟议的实验中使用。使用 这些方法应该可以描述精神运动 可卡因的效果，其精确度是迄今为止从未达到的。在……里面 除了行为分析，总脑重测量 将对所有EC和IC大鼠以及选定的 受试者，将在额部进行儿茶酚胺分析 皮质和伏隔核。总而言之，拟议的 行为、药理学和中枢神经系统分析应该提供 关于行为后果的重要新信息 可卡因的使用。

The proposed work will investigate the effects of behaviorally relevant differential rearing histories on rats' responsiveness to cocaine, where responsiveness is defined in terms of the discriminative stimulus properties of cocaine and in terms of cocaine's capacity to enhance or disrupt psychomotor performance. Rats with demonstrably different behavioral and neural attributes will be prepared by exposing half of the rats to an enriched rearing environment (EC for enriched condition) and the other half to an impoverished environment (IC for isolated or impoverished condition) for 60 days after weaning. The effects of these profoundly different histories will be assessed in two-lever saline-cocaine discrimination tasks. Responsiveness to cocaine as a discriminative stimulus will be quantitated by the speed of learning the discrimination, by the dose of cocaine that can successfully serve as a discriminative stimulus, and by the lowest dose to which the discriminative behavior generalizes. In addition to comparing the performance of IC and EC rats in a cocaine- saline discrimination paradigm, the proposed work will also determine whether rearing history affects the degree to which rats generalize from the cocaine training cue to other drugs with high abuse liability (d-amphetamine, fentanyl, phencyclidine, midazolam, and MDMA ("Ecstasy")). D1 (SCH23390) and D2 (sulpiride) dopamine receptor blockers will also be evaluated for their capacity to block the cocaine cue. The effects of EC and IC rearing on responsiveness to cocaine's psychomotor effects will be assessed by conducting a dose-response analysis based on operant performance maintained under conditions of high or low effort demand. Operant force measurement methods, which permit the recording of the peak force and duration of every response (including subcriterion responses not detectable by conventional methods), will be used in all the proposed experiments. With these methods it should be possible to describe the psychomotor effects of cocaine with a precision not heretofore achieved. In addition to the behavioral analyses, total brain weight measures will be taken for all EC and IC rats, and for a selected sample of subjects, catecholamine analyses will be performed on frontal cortex and nucleus accumbens. Taken together, the proposed behavioral, pharmacological and CNS analyses should provide important new information on the behavioral consequences of cocaine use.