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采用多元分析法评估大鼠在寻求刺激和冲动性方面的个体差异,以及这些差异对安非他命自我给药和前额叶多巴胺功能的预测作用。

A multivariate assessment of individual differences in sensation seeking and impulsivity as predictors of amphetamine self-administration and prefrontal dopamine function in rats.

机构信息

Discovery and Analytical Sciences, RTI, International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.

出版信息

Exp Clin Psychopharmacol. 2011 Aug;19(4):275-84. doi: 10.1037/a0023897.

Abstract

Drug abuse vulnerability has been linked to sensation seeking (behaviors likely to produce rewards) and impulsivity (behaviors occurring without foresight). Since previous preclinical work has been limited primarily to using single tasks as predictor variables, the present study determined if measuring multiple tasks of sensation seeking and impulsivity would be useful in predicting amphetamine self-administration in rats. Multiple tasks were also used as predictor variables of dopamine transporter function in the medial prefrontal and orbitofrontal cortexes, as these neural systems have been implicated in sensation seeking and impulsivity. Rats were tested on six behavioral tasks as predictor variables to evaluate sensation seeking (locomotor activity, novelty place preference, and sucrose reinforcement on a progressive ratio schedule) and impulsivity (delay discounting, cued go/no-go, and passive avoidance), followed by d-amphetamine self-administration (0.0056-0.1 mg/kg infusion) and kinetic analysis of dopamine transporter function as outcome variables. The combination of these predictor variables into a multivariate approach failed to yield any clear relationship among predictor and outcome measures. Using multivariate approaches to understand the relation between individual predictor and outcome variables in preclinical models may be hindered by alterations in behavior due to training and thus, the relation between various individual differences in behavior and drug self-administration may be better assessed using a univariate approach in which a only a single task is used as the predictor variable.

摘要

药物滥用易感性与寻求刺激(可能产生奖励的行为)和冲动(无远见的行为)有关。由于以前的临床前工作主要局限于使用单一任务作为预测变量,因此本研究旨在确定测量多个寻求刺激和冲动的任务是否有助于预测大鼠的安非他命自我给药。还使用多种任务作为内侧前额叶皮层和眶额皮层多巴胺转运蛋白功能的预测变量,因为这些神经系统与寻求刺激和冲动有关。大鼠在六个行为任务上进行测试,作为预测变量来评估寻求刺激(运动活动、新奇地点偏好和蔗糖强化递增比率方案)和冲动(延迟折扣、线索 Go/No-Go 和被动回避),然后进行安非他命自我给药(0.0056-0.1mg/kg 输注)和多巴胺转运蛋白功能的动力学分析作为结果变量。这些预测变量的组合成多元方法未能在预测和结果测量之间产生任何明确的关系。使用多元方法来理解临床前模型中个体预测和结果变量之间的关系可能会受到由于训练而导致的行为改变的阻碍,因此,使用单变量方法(仅使用一个任务作为预测变量)可能更能评估行为的各种个体差异与药物自我给药之间的关系。

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