Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.

Excessive alcohol use is often associated with accelerated cognitive decline, and extensive research using animal models of human alcohol consumption has been conducted into potential mechanisms for this relationship. Within this literature there is considerable variability in the types of models used. For example, alcohol administration style (voluntary/forced), length and schedule of exposure and abstinence period are often substantially different between studies. In this review, we evaluate recent research into alcohol-induced cognitive decline according to methodology of alcohol access, as well as cognitive behavioral task employed. Our aim was to query whether the nature and severity of deficits observed may be impacted by the schedule and type of alcohol administration. We furthermore examined whether there is any apparent relationship between the amount of alcohol consumed and the severity of the deficit, as well as the potential impact of abstinence length, and other factors such as age of administration, and sex of subject. Over the past five years, researchers have overwhelmingly used non-voluntary methods of intake, however deficits are still found where intake is voluntary. Magnitude of intake and type of task seem most closely related to the likelihood of producing a deficit, however even this did not follow a consistent pattern. We highlight the importance of using systematic and clear reporting styles to facilitate consistency across the literature in this regard. We hope that this analysis will provide important insights into how experimental protocols might influence findings, and how different patterns of consumption are more or less likely to produce an addiction-vulnerable cognitive phenotype in animal models.