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，其特征是被认为是“冲动”的行为。冲动性通常被定义为选择一个小的、直接的结果或强化物，而不是一个更大的、更延迟的结果，即自我控制的选择。冲动选择可能是由于较大的强化物的价值由于其呈现的延迟而被贴现的结果。事实表明，药物滥用者比非药物滥用者更不重视延迟结果的价值。然而，目前尚不清楚延迟折扣或冲动选择是一种急性药物效应，是长期药物暴露的结果，还是由行为史或基因决定的个人行为曲目的预先存在的组成部分。目前的提案旨在开始解决这些问题，通过研究药物滥用对冲动选择的急性和慢性影响，在动物模型中使用两种不同的大鼠品系，Lewis和Fischer 344，这两种品系在潜在相关的神经化学和行为测量上存在差异。该研究有两个特定的目标，在两个系列的实验中得到解决。具体目的1是研究药物滥用对两种大鼠冲动选择的急性影响，这两种大鼠的冲动选择可能存在差异。具体目的2是研究反复给药（长期暴露）对两种大鼠冲动选择的影响。冲动选择和药物效应的差异和系统发现将为进一步研究理解延迟折扣和冲动选择中神经化学和遗传学的作用奠定基础。本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、多动症和其他危险行为，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.