Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking

Abstract

Alcohol use disorder (AUD) is characterized by impairments in decision‐making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision‐making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre‐existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set‐shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision‐making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables—in this case, impaired cognitive flexibility and heightened urgency, respectively—may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.

Individual differences in behavioral flexibility predict future volitional ethanol consumption in mice

“…Resistance to change behavior in light of changing environmental conditions is an underlying component to both excessive alcohol consumption and a decreased behavioral flexibility. This supports previous findings across species that repetitive habitual behavior is associated with increased EtOH consumption in primates and alcohol preferring rats (De Falco et al, 2021; Shnitko et al, 2019). Evidence of this relationship in a rat strain specifically bred for high alcohol preference supports a biological basis underlying these co-occurring traits with potentially shared genetic and/or neural origins.…”

“…It has been reported in humans and animal models that chronic alcohol consumption induces cognitive impairments in executive functioning (Bernardin, Maheut-Bosser, & Paille, 2014; Houston et al, 2014; Rodberg et al, 2017; Trick et al, 2014). This study, and others, have shown that decreased baseline cognitive ability is associated with higher levels of individual alcohol consumption (De Falco et al, 2021; Shnitko et al, 2019). Performance on ASST can be used as a readout of cognitive disruption to both predict proclivity to consume large amounts of alcohol and to measure cognitive deficits caused by alcohol consumption.…”

“…Decreased executive functioning, cognition, and behavioral flexibility has been frequently demonstrated in humans, primate, and rodents as a consequence of excessive alcohol use (Gass et al, 2014; Houston et al, 2014; Kroener et al, 2012; Rodberg et al, 2017; Shnitko, Gonzales, Newman, & Grant, 2020; Trick, Kempton, Williams, & Duka, 2014). Recently, an association between lower behavioral flexibility and the likelihood of future heavy drinking has been identified in non-human primates and rats (De Falco et al, 2021; Shnitko, Gonzales, & Grant, 2019) but it is not clear whether this prospective relationship is seen in other models of alcohol use. Behavioral flexibility as a potential predictive factor that is further impacted by excessive alcohol intake suggests an important bidirectional relationship with alcohol consumption.…”

Distinct cortico-striatal compartments drive competition between adaptive and automatized behavior

“…Work from our group shows that outcome representations are reduced in animals that drink alcohol compulsively, and also demonstrate impaired behavioral flexibility (De Falco et al, 2021; Linsenbardt et al, 2019; Timme et al, 2021). More specifically, reductions in mutual information about two competing options was observed in neural recordings obtained from the mPFC of rats that drink alcohol compulsively, indicating that the representation of these options was not clearly disambiguated.…”

Childhood trauma, stressful life events, and depression: Exploring the mediating effect of cognitive flexibility.

“…Cognitive flexibility is one of the vulnerability factors related to depression (Stange et al, 2017). In addition, cognitive flexibility is not only a relatively stable trait formed by the influence of childhood experiences during the process of growing up (De Falco et al, 2021; Legare et al, 2018) but also a state that will change with stress exposure (Anacker & Hen, 2017; Shields et al, 2016). Therefore, cognitive flexibility may play an important mediating role in the process of childhood trauma and stressful life events affecting depression.…”