REARING HISTORY AND BEHAVIORAL RESPONSIVENESS TO COCAINE

拟议的工作将调查行为的影响， 相关差异饲养史对大鼠对 可卡因，其中反应性是根据 可卡因的辨别刺激特性， 可卡因增强或破坏精神的能力 性能 具有明显不同行为和 通过将一半大鼠暴露于 丰富的饲养环境（EC为丰富的条件）和 另一半是贫困的环境（IC为孤立或 贫困条件）断奶后60天。 的影响 这些深刻不同的历史将在两个层面进行评估， 盐水可卡因辨别任务。 对可卡因的反应， 辨别刺激将通过以下速度来量化： 通过可卡因的剂量， 成功地作为一个歧视性的刺激，并通过最低的 歧视性行为普遍化的剂量。 此外 来比较IC和EC大鼠在可卡因中的表现- 盐水歧视范例，拟议的工作也将 确定养育史是否影响 大鼠从可卡因训练线索泛化到其他药物， 高滥用倾向（d-安非他明，芬太尼，苯环利定， 咪达唑仑和MDMA（“摇头丸”））。 D1（SCH 23390）和D2 （舒必利）多巴胺受体阻滞剂也将进行评估， 他们阻断可卡因线索的能力 EC和IC的影响 对可卡因的精神影响的反应性的饲养将是 通过基于操作性的剂量反应分析进行评估 在高或低努力条件下保持的性能 需求 操作力测量方法，允许 记录每次响应的峰值力和持续时间 （包括常规方法检测不到的次标准反应） 方法），将用于所有拟议的实验。 与 这些方法应该可以描述 可卡因的精确效果，迄今为止还没有达到。 在 除了行为分析，总脑重量测量 将对所有EC和IC大鼠进行采集，并对选定的 受试者，将对额叶进行儿茶酚胺分析。 皮层和背侧核。 综合考虑， 行为、药理学和CNS分析应提供 重要的新信息的行为后果 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.