Effects of abused drugs and genetics on impulsive choice

描述(申请人提供)：许多精神障碍，包括药物滥用，都以被认为是“冲动”的行为为特征。冲动性通常被定义为选择一个小的、直接的结果或强化，而不是一个更大的、更延迟的结果，即自我控制的选择。冲动的选择可能是由于较大的增强剂的价值由于其呈现的延迟而被打折的结果。事实表明，吸毒者比非吸毒者在更大程度上对延迟结果的价值打折扣。然而，目前尚不清楚延迟打折或冲动选择是急性药物效应，还是长期接触药物的结果，还是由行为史或遗传学决定的个人行为体系中预先存在的组成部分。本提案旨在通过使用两个不同的大鼠品系Lewis和Fischer 344在动物模型中调查滥用药物对冲动选择的急性和慢性影响来开始解决这些问题，这两个品系在潜在相关的神经化学和行为测量方面存在差异。这项研究有两个具体的目标，在两个系列的实验中得到了解决。具体目标1是调查滥用药物对两个品系大鼠冲动选择的急性影响，预计这两个品系的大鼠在冲动选择方面会有所不同。具体目标2是检查反复给药(长期暴露)滥用药物对两种大鼠品系冲动选择的影响。在冲动选择和药物效应方面的不同和系统的发现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滥用药物的影响。归根结底，这项工作可能与许多以冲动行为为特征的疾病有关，如药物滥用、赌博、暴力、ADHD和其他危险行为，如可能导致艾滋病毒/艾滋病传播的共用针头。

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.