Effects of abused drugs and genetics on impulsive choice

描述（由申请人提供）：许多精神疾病，包括药物滥用，其特征是行为被认为是“冲动的”。冲动性通常被定义为选择一个小的，立即的结果，或者选择一个更大的，更延迟的结果，自我控制的选择。冲动的选择可能是由于延迟呈现而使较大的股票价值被打折的结果。药物滥用者比非药物滥用者在更大程度上低估了延迟结果的价值。然而，目前尚不清楚延迟折扣或冲动选择是否是一种急性药物效应，长期药物暴露的后果，或由行为史或遗传学决定的个体行为库的预先存在的组成部分。本提案旨在开始，以解决这些问题的急性和慢性影响的药物滥用的冲动选择的动物模型，使用两种不同的大鼠品系，刘易斯和费舍尔344，不同的潜在相关的神经化学和行为的措施。该研究有两个具体目标，在两个系列的实验中解决。具体目的1是调查急性影响的药物滥用冲动的选择，在两个大鼠品系，这是预期不同的冲动的选择。具体目标2是检查重复给药（长期暴露）滥用药物对两种大鼠冲动选择的影响。冲动选择和药物效应的差异性和系统性研究结果将为进一步研究神经化学和遗传学在延迟折扣和冲动选择中的作用奠定基础。这项研究将有助于理解延迟折扣和冲动选择的神经行为生物学以及药物滥用的影响。最终，这项工作可能与许多以冲动行为为特征的疾病有关，例如药物滥用，赌博，暴力，ADHD和其他危险行为，例如，共用针头可能导致艾滋病毒/艾滋病的传播。

DESCRIPTION (provided by applicant): Many psychiatric disorders, including drug abuse, are characterized by behavior that is deemed "impulsive." Impulsivity is often defined as the choice for a small, immediate outcome or reinforcer over a larger, more delayed outcome, the self-controlled choice. Impulsive choices may be a result of the value of the larger reinforcer being discounted due to the delay to its presentation. Drug abusers have been shown to discount the value of delayed outcomes to a greater extent than non-drug abusers. However, it is not clear whether delay discounting or impulsive choice is an acute drug effect, a consequence of long-term drug exposure, or a pre-existing component of an individual's behavioral repertoire determined by behavioral history or genetics. The present proposal is designed to begin to address these issues by the investigation of acute and chronic effects of drugs of abuse on impulsive choice in an animal model using two different rat strains, Lewis and Fischer 344, which differ in potentially relevant neurochemical and behavioral measures. The research has two Specific Aims that are addressed in two series of experiments. Specific Aim 1 is to investigate acute effects of drugs of abuse on impulsive choice in the two rat strains, which are expected to differ in their impulsive choices. Specific Aim 2 is to examine effects of repeated administration (long-term exposure) of drugs of abuse on impulsive choice in the two rat stains. Differential and systematic findings in impulsive choice and drug effects will lay the foundation for further studies into understanding the role of neurochemistry and genetics into delay discounting and impulsive choice. The proposed research will contribute to the understanding of the neurobehavioral biology of delay discounting and impulsive choice and effects of drugs of abuse. Ultimately, this work may have relevance to many disorders characterized by impulsive behavior such as, drug abuse, gambling, violence, ADHD, and other risky behaviors, e.g., sharing needles that may result in the spread of HIV/AIDS.