Memory effects of stimulant drugs in humans

描述（由申请人提供）：最近的药物滥用理论表明，成瘾涉及异常的记忆处理。在非人类中，兴奋剂促进编码和检索过程，其中任何一个都可能影响未来的药物寻求行为。在人类中，觉醒或情绪的主观状态会使情绪记忆产生偏差，这就增加了产生这些状态的药物也可能使记忆产生偏差，从而影响吸毒的可能性。滥用药物对记忆的影响尚未在人类中仔细研究。在这项探索性研究中，我们建议检查的影响，d-安非他明（AMP）的编码和检索过程，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是否有助于随后在无药物状态下评估的检索？2)在提取时给予AMP是否能改善对先前在无药物状态下编码的刺激的记忆？3)如果个体在编码和提取过程中处于相同的状态（AMP或安慰剂），与在编码或提取过程中接受AMP相比，提取是否会增强？本研究将在健康年轻成人（N=60）中采用四阶段受试者内设计。每次会话包括两个阶段，编码阶段，48小时后是检索阶段。在所有四种组合中编码或检索之前，受试者将接受含有AMP（20 mg）或安慰剂的胶囊。在编码阶段，受试者将观看或研究具有情绪积极、消极和中性内容的标准化刺激，并且在48小时后的提取阶段期间评估他们对刺激的记忆。基于实验室动物的研究结果，我们假设AMP在编码或提取过程中会促进对情感内容刺激的记忆。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，记忆将最大化。这里研究的记忆过程对寻找药物有重要的影响。觅药行为受到对先前事件的记忆的强烈影响，在编码或提取过程中药物诱导的偏差可能会深刻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求行为的影响奠定基础。 公共卫生相关性：有人认为滥用药物是一种记忆障碍。也就是说，滥用药物会在药物与刺激物和与其使用相关的事件之间产生异常强烈、有弹性的记忆，这些记忆和关联会促进未来的药物使用。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。这些影响尚未在人类中进行过研究。在这里，我们将研究原型兴奋剂安非他明的编码和检索的显着，情感刺激在健康志愿者的影响。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.