DOPAMINERGIC MECHANISMS OF INTERVAL TIMING & DRUG ABUSE

描述（由申请人提供）：本提案的主要目标是 评估条件刺激的特征对 滥用药物在一类行为背景下的影响， 准确反映醉酒程度：计时在秒到分钟 范围虽然基本的行为过程，如学习， 计算和决策主要依赖于估计和再现 滥用药物会导致时间知觉的扭曲。 多巴胺（DA）激动剂（例如，甲基苯丙胺（AMP）导致行为 与内部时钟的加速一致，而DA拮抗剂 (e.g.,氟哌啶醇（Haloperidol，HAL）导致的行为与减缓 时钟虽然有可能一些强化和成瘾 DA受体激动剂的性质可能与其对内源性多巴胺受体的作用有关。 时钟，证据表明，DA也可能有助于注意力或预测 功能协调发展的因此，除了与时钟相关的效应之外，DA 药物可能会通过影响过滤或 事件的预测。本提案中所述的实验旨在 分离DA的记忆效应、时钟效应和注意力效应 在大鼠动物模型中，由于DA 神经精神药理学在大鼠和人类中非常相似。的主要目标 （1）制定一套评估程序， 条件刺激的特性对时间和记忆的影响 时机通过对比“空”和“满”间隔的时间， 将注意力与时钟和记忆效应分离。模态偏差将是 通过使用听觉或视觉定时线索进行检查。(2)以解离 AMP和HAL的注意力和时钟效应，通过评估它们对 定时大鼠的“空”和“满”间隔。没有研究表明 DA药物对定时“空”间期的影响。剂量反应曲线将为 对于AMP和HAL两者建立（每种药物三种药物剂量）。(3)到 分离AMP和HAL对间隔计时的时钟和注意力效应， 通过研究另一事件（间隙）对定时间隔的中断。的 实验将分离时钟（左移/右移）和注意力 （复位/停止）AMP和HAL的影响。目前还没有关于多巴胺 对记忆进行计时的药物“空”间隔或间隔间隙。在一起， 这些研究将为当前的计时、时间感知和DA模型提供信息 精神药理学它们将有助于阐明 间隔时间和了解的影响的特点 药物滥用对时间知觉扭曲的注意线索

DESCRIPTION (provided by applicant): The main goal of this proposal is to evaluate the impact of the characteristics of conditioned stimuli on the effects of abuse drugs in the context of a class of behaviors that was shown to accurately reflect the degree of intoxication: timing in the seconds-to-minutes range. While fundamental behavioral processes such as learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals, drugs of abuse result in distortions of time perception. Dopamine (DA) agonists (e.g., methamphetamine, AMP) result in behavior consistent with a speeding up of the internal clock, while DA antagonists (e.g., haloperidol, HAL) result in behavior consistent with a slowing of the clock. While there is the possibility that some reinforcing and addiction properties of DA agonists might be related to their effects on the internal clock, evidence suggests that DA might also serve attentional or predictive functions. It is therefore possible that besides clock-related effects, DA drugs might distort time perception indirectly by affecting the filtering or prediction of events. The experiments described in this proposal aim at dissociating the memory effects, clock-effects, and attentional effects of DA drugs on interval timing in the rat animal model, because DA neuropsychopharmacology is very similar in rats and humans. The main goals of the project are as follows: (1) To develop a set of procedures to evaluate the impact of the characteristics of conditioned stimuli on timing and memory for timing. By contrasting the timing of "empty" and "filled" intervals one can dissociate attentional from clock and memory effects. The modality bias will be examined by using auditory or visual timed cues. (2) To dissociate the attentional and clock effects of AMP and HAL by evaluating their effect on timing "empty" and "filled" intervals in rats. There are no studies of the effects of DA drugs on timing "empty" intervals. Dose response curves will be established for both AMP and HAL (three drug doses for each drug). (3) To dissociate the clock and attentional effects of AMP and HAL on interval timing, by studying the interruption of the timed interval by another event (gap). The experiments will dissociate the clock (shift left/right) and attentional (reset/stop) effects of AMP and HAL. There are no studies of the effects of DA drugs on memory for timing "empty" intervals or intervals with gaps. Together, the studies will inform current models of timing, time perception, and DA psychopharmacology. They will help elucidate the pharmacological basis of interval timing and understand the impact of the characteristics of the attentional cues on the distortions of time perception by drugs of abuse.