REARING HISTORY AND BEHAVIORAL RESPONSIVENESS TO COCAINE

可卡因的饲养史和行为反应

• 批准号: 3211574
• 负责人: STEPHEN Cletius FOWLER
• 金额: $ 8.61万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211574
• 关键词: anesthetics; behavior test; catecholamine inhibitor; central nervous system stimulants; cocaine; dextroamphetamine; discrimination learning; dopamine receptor; dosage; early experience; fentanyl; frontal lobe /cortex; isolation /deprivation; laboratory rat; nucleus accumbens; operant conditionings; phencyclidine; psychological reinforcement; psychomotor function; psychopharmacology; psychotomimetic drug; socioenvironment; stimulus generalization

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.

拟议的工作将调查行为的影响 相关差异饲养史对大鼠反应性的影响 可卡因，其中反应性是根据 可卡因的歧视性刺激特性 可卡因增强或破坏精神运动的能力 表现。 具有明显不同行为和特征的老鼠 将一半的老鼠暴露于 丰富的饲养环境（EC 表示丰富的条件）和 另一半到贫困的环境（IC用于孤立或 断奶后60天。 的影响 这些截然不同的历史将通过两个杠杆进行评估 盐水-可卡因辨别任务。 对可卡因的反应 区别性刺激将通过速度来量化 通过可卡因的剂量来了解歧视 成功地作为一种歧视性刺激，并且由最低的 歧视行为普遍化的剂量。 此外 比较 IC 和 EC 大鼠在可卡因中的表现 盐水歧视范式，拟议的工作也将 确定饲养历史是否影响其程度 老鼠从可卡因训练线索泛化到其他药物 高滥用倾向（d-苯丙胺、芬太尼、苯环己哌啶、 咪达唑仑和 MDMA（“摇头丸”））。 D1 (SCH23390) 和 D2 （舒必利）多巴胺受体阻滞剂也将被评估 他们阻止可卡因提示的能力。 EC和IC的影响 培养对可卡因精神运动效应的反应 通过基于操作的剂量反应分析进行评估 在高努力或低努力的条件下保持绩效 要求。 操作力测量方法，允许 记录每次反应的峰值力和持续时间 （包括传统方法无法检测到的次标准响应 方法），将用于所有建议的实验。 和 这些方法应该可以描述精神运动 可卡因的效果达到了前所未有的精确度。 在 除了行为分析之外，还测量大脑总重量 将对所有 EC 和 IC 大鼠以及选定的样本进行采集 受试者，儿茶酚胺分析将在额叶进行 皮质和伏隔核。 综合起来，建议 行为、药理学和中枢神经系统分析应提供 关于行为后果的重要新信息 使用可卡因。