Attentional bias to alcohol cues in rats: development and decline

描述（由申请人提供）：使用注意力偏差程序评估人类对酒精相关刺激（酒精线索）的注意力，（a）可能干扰重度饮酒者的其他活动，（B）与问题饮酒的模式和严重程度有关，（c）在当前饮酒者中比在恢复中的饮酒者更大。 这一证据表明，减少对酒精线索的注意偏差的疗法可能会防止线索诱导的复发。 相反，有效的治疗也可能通过促进禁欲来减少注意力偏差。 更好地理解注意偏向变化的机制可以阐明注意偏向与复发之间的关系。 注意力偏差的临床前模型将有助于此类研究。 在这里，我们开发了一个动物模型的人类注意力偏差的程序，参加酒精线索干扰识别的目标。 在这个项目中，老鼠被训练去注意发出信号的刺激，以及何时对食物做出反应（食物刺激）。 刺激呈现是短暂的，并且不正确或遗漏的反应通过扣留食物奖励来惩罚。 一旦大鼠学会了这个连续反应时间（SRT）任务，我们就在单独的会话中将音调（酒精提示）与酒精传递配对。 最终，大鼠将注意到酒精提示，但不是另一个（控制提示）在SRT会话，这将是显而易见的，从延迟的相对增加，以正确的反应，并在不正确的或省略的反应，在酒精与控制提示介绍。 我们首先确定如何增加注意力需求的SRT任务的影响酒精提示介绍的效果，通过减少食物刺激介绍的持续时间（目标1）。 这允许为后续研究进行参数优化。 然后，我们研究如何增加酒精+酒精提示配对会话的数量影响干扰SRT性能的酒精提示介绍（目的2）。 这与人类文献相一致，人类文献表明，与偶尔饮酒者相比，重度饮酒者的注意力偏差更大。 最后，我们确定如何灭绝（酒精提示是没有酒精）影响干扰SRT性能的酒精提示介绍（目的3）。 我们将这些结果与具有匹配的暂停暴露期（既不存在酒精也不存在线索）的大鼠的结果进行比较。 这将解决是否治疗，减少注意力偏差酒精线索可能会提供保护，防止复发，减少注意酒精线索在熟悉的环境中遇到，然后沉淀复发。 不针对酒精线索而仅强制戒酒的治疗可能无法提供这种额外的保护。 这些实验建立了一个新颖的，创新的，翻译的临床前模型的临床注意力偏差的程序。 这将有助于今后的研究 将注意偏差的临床观察与条件接近或工具反应的临床前观察相关联。 这些研究也将促进未来对酒精线索的注意力偏差的神经生物学机制的研究，并可以确定更有效的治疗方法来防止复发。

DESCRIPTION (provided by applicant): Attending to alcohol-associated stimuli (alcohol cues) is assessed in humans using attentional bias procedures and (a) can interfere with other activities in heavy drinkers, (b) is related to the pattern and severity of problematic drinking, nd (c) is greater among current drinkers versus those in recovery. This evidence suggests that therapies that decrease attentional bias to alcohol cues might prevent cue-induced relapse. Conversely, it is also possible that effective therapies decrease attentional bias by facilitating abstinence. Better understanding the mechanisms responsible for changes in attentional bias could elucidate the relationship between attentional bias and relapse. Such research would be facilitated by a preclinical model of attentional bias. Here we develop an animal model of the human attentional bias procedure, where attending to alcohol cues interferes with the identification of a target. In this project, rats are trained to attend to stimuli that signal whee and when to respond for food (food stimuli). Stimulus presentation is brief, and incorrect or omitted responses are penalized by withholding food reward. Once rats learn this serial reaction time (SRT) task, we pair a tone (alcohol cue) with alcohol delivery in separate sessions. Ultimately, rats will attend to the alcohol cue, but not another (control cue) during an SRT session, which will be evident from a relative increase in latency to correct responses and in incorrect or omitted responses during alcohol versus control cue presentation. We first determine how increasing the attentional demand of the SRT task influences the effect of alcohol cue presentation by decreasing the duration of the food stimuli presentations (Aim 1). This allows parameter optimization for subsequent studies. We then examine how increasing the number of alcohol + alcohol-cue pairing sessions affects interference with SRT performance by alcohol cue presentation (Aim 2). This would be consistent with human literature demonstrating greater attentional bias among heavier versus occasional drinkers. Finally, we determine how extinction (where the alcohol cue is presented without alcohol) affects interference with SRT performance by alcohol cue presentation (Aim 3). We compare these results to those from rats with a matched period of suspended exposure (where neither alcohol or the cue are present). This will address whether treatments that decrease attentional bias to alcohol cues might provide protection against relapse by reducing attention to alcohol cues encountered in familiar environments and then precipitate relapse. Treatments that do not target attending to alcohol cues but instead only impose abstinence may not provide this additional protection. These experiments establish a novel, innovative, and translational preclinical model of the clinical attentional bias procedure. This will facilitate future studies relating clinical observations of attentional bias to preclinical observations of conditioned approach or instrumental responding. These studies will also facilitate future investigation of neurobiological mechanisms of attentional bias to alcohol cues and could identify more effective therapies to prevent relapse.