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，兴奋剂促进了编码和检索过程，这两者中的任何一个都可能影响未来的药物寻求行为。在人类中，已知觉醒或情绪的主观状态会影响情绪记忆，因此产生这些状态的药物可能也会影响记忆，从而影响吸毒。滥用药物对人类记忆的影响还没有被仔细研究过。在这项探索性研究中，我们建议研究d-安非他明（AMP）对编码和检索过程的影响，重点是情绪记忆。我们将解决三个主要问题：1)在编码时使用AMP是否有助于在无药状态下进行后续检索评估？2)在检索时给予AMP是否能改善先前在无药物状态下编码的刺激记忆？3)如果个体在编码和检索过程中处于相同的状态（AMP或安慰剂），与在编码或检索过程中接受AMP相比，检索是否增强？该研究将在健康的年轻成人（N=60）中采用四期的主题内设计。每个会话由两个阶段组成，一个是编码阶段，48小时后是检索阶段。受试者将在编码或检索前接受含有AMP （20mg）或安慰剂的胶囊。在编码阶段，受试者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小时后的检索阶段评估其对刺激的记忆。基于实验动物的发现，我们假设在编码或检索过程中使用AMP会促进对含有情绪内容的刺激的记忆。基于人类对唤醒和情绪一致性的研究，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，我们假设当编码和检索发生在相同的状态（药物或非药物）时，记忆将最大化。本文研究的记忆过程对药物寻求具有重要意义。药物寻求行为强烈地受到先前事件记忆的影响，并且在编码或检索过程中药物引起的偏见可能深刻地影响未来的药物使用。这个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。

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.