Attentional Bias to Alcohol Cues in Rats: Development and Decline

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. PUBLIC HEALTH RELEVANCE: Project Narrative Alcohol-associated cues grab the attention of heavy drinkers, and it is thought that this may lead to craving and relapse. Those in recovery pay less attention to alcohol cues which could reflect a mechanism of effective therapy, or it could simply follow from longer periods of abstinence; however, this is difficult to determine in humans or current animal models. In this project, we will develop an animal model of attentional bias to alcohol cues so that the relation between this attentional bias and heavy drinking can be studied.