Memory effects of stimulant drugs in humans

描述(由申请者提供)：最近的药物滥用理论表明，成瘾与异常记忆处理有关。在非人类中，刺激性药物促进了编码和检索过程，这两个过程中的任何一个都可能影响未来的药物寻找行为。在人类中，已知的唤醒或情绪的主观状态会偏向情绪记忆，这增加了产生这些状态的药物也可能偏向记忆，从而影响吸毒的可能性。滥用药物对记忆的影响还没有在人类身上仔细研究过。在这项探索性研究中，我们建议检查d-苯丙胺(AMP)对编码和提取过程的影响，重点是情绪记忆。我们将解决三个主要问题：1)在编码时给予AMP是否促进了在非药物状态下评估的后续检索？2)在检索时给予AMP是否改善了对先前在非药物状态下编码的刺激的记忆？3)与在编码或检索期间接受AMP相比，如果个体在编码和检索期间处于相同的状态(AMP或安慰剂)，检索能力是否增强？这项研究将在健康的年轻人(N=60)中使用四个疗程的受试者内设计。每个会话由两个阶段组成，即编码阶段，48小时后是检索阶段。受试者将接受含有AMP(20毫克)或安慰剂的胶囊，然后以所有四种组合进行编码或检索。在编码阶段，受试者将观看或学习具有情绪积极、消极和中性内容的标准化刺激，并在48小时后的提取阶段评估他们对刺激的记忆。根据对实验动物的研究结果，我们假设在编码或提取过程中使用AMP将促进对带有情绪内容的刺激的记忆。基于对唤醒和情绪一致性的人类研究，我们进一步假设，记忆促进可能与药物增加唤醒或积极情绪状态的潜力有关。最后，基于状态依赖学习的证据，我们假设，当编码和提取发生在相同的(药物或非药物)状态时，记忆将被最大化。这里研究的记忆过程对寻找毒品有重要的影响。寻找毒品的行为受到对以前事件的记忆的强烈影响，在编码或提取过程中的药物诱导偏见可能会深刻地影响未来的药物使用。该项目将为未来研究记忆偏差对药物寻找行为的影响奠定基础。 与公共健康相关：有人认为药物滥用是一种记忆障碍。也就是说，滥用药物在药物与刺激和与其使用相关的事件之间创造了异常强烈的、有弹性的记忆，这些记忆和联系促进了未来的药物使用。对非人类的研究支持这一观点，表明药物直接促进和增强了对显著刺激的学习。这些影响还没有在人类身上进行过研究。在这里，我们将研究典型兴奋剂苯丙胺对健康志愿者显著情感刺激编码和提取的影响。这项研究将为未来研究药物如何以及为什么增强情绪记忆，以及记忆增强如何影响药物寻求行为奠定基础。

DESCRIPTION (provided by applicant): Recent theories of drug abuse suggest that addiction involves aberrant memory processing. In nonhumans, stimulant drugs facilitate both encoding and retrieval processes, either of which could influence future drug-seeking behavior. In humans, subjective states of arousal or mood are known to bias emotional memory, raising the possibility that drugs producing these states may also bias memory and thereby influence drug-taking. The effects of drugs of abuse on memory have not been carefully studied in humans. In this exploratory study we propose to examine the effects of d-amphetamine (AMP) on encoding and retrieval processes, with a focus on emotional memory. We will address three main questions: 1) does AMP administered at the time of encoding facilitate subsequent retrieval assessed in a drug free state? 2) does AMP administered at the time of retrieval improve memory for stimuli previously encoded in a drug-free state? 3) is retrieval enhanced if the individual is in the same state (AMP or placebo) during both encoding and retrieval, compared to receiving AMP during either encoding or retrieval? The study will use a four-session within-subject design in healthy young adults (N=60). Each session consists of two phases, an encoding phase, followed 48 hours later by a retrieval phase. Subjects will receive capsules containing AMP (20 mg) or placebo before encoding or retrieval in all four combinations. During the encoding phases subjects will view or study standardized stimuli with emotionally positive, negative and neutral content, and their memory for the stimuli will be assessed 48 hours later during the retrieval phase. Based on findings with laboratory animals, we hypothesize that AMP administered during either encoding or retrieval will facilitate memory for stimuli with emotional content. Based on human studies of arousal and mood-congruence, we further hypothesize that memory facilitation may be related either to the drug's potential to increase either arousal or positive mood states. Finally, based on evidence for state-dependent learning, we hypothesize that memory will be maximized when encoding and retrieval take place in the same (drug or no-drug) state. The memory processes studied here have important consequence for drug-seeking. Drug-seeking behavior is strongly influenced by memory of previous events, and drug- induced biases during either encoding or retrieval could profoundly influence future drug use. This project will form the basis for future investigations of the effects of memory biases on drug-seeking behavior. PUBLIC HEALTH RELEVANCE: It has been argued that drug abuse is a disorder of memory. That is, drugs of abuse create unusually strong, resilient memories between the drug and the stimuli and events associated with their use, and these memories and associations promote future drug use. Studies with nonhumans support this idea, showing that drugs directly facilitate and enhance the learning of salient stimuli. These effects have not yet been studied in humans. Here, we will investigate the effect of the prototypic stimulant amphetamine on encoding and retrieval of salient, affective stimuli in healthy volunteers. This study will form the basis of future research on how and why drugs enhance emotional memory, and how memory-enhancement influences drug-seeking behavior.