Habitual Ethanol Seeking and Licking Microstructure of Enhanced Ethanol Self‐Administration in Ethanol‐Dependent Mice

Abstract

Background: A significant component of ethanol (EtOH) dependence is the disruption to decision-making processes. Prior work has shown EtOH dependence biases habitual seeking of EtOH and disrupts neural mechanisms supporting decision-making. This has contributed to the hypothesis that habitual EtOH seeking in EtOH dependence may promote excessive habitual or compulsive EtOH consumption. However, decision-making and behavioral processes underlying seeking and consummatory behaviors differ. Here, we examine the microstructure of EtOH consummatory behavior in the context of habitual EtOH seeking.Methods: Following home cage pre-exposure to EtOH, C57Bl/6J mice underwent 4 rounds of chronic intermittent EtOH (CIE) or air exposure. Following acute withdrawal, mice began training for operant self-administration of 15% EtOH. Training consisted of 16-hour sessions in which mice were trained in a random ratio (RR) schedule of reinforcement for 30-second access to the EtOH sipper. To test for CIE-induced changes in action control, we used sensory-specific satiation and assessed the effect of outcome devaluation on EtOH seeking. Importantly, the use of a lickometer during operant training allowed us to measure the microstructure of lick behavior.Results: Prior induction of EtOH dependence led to increased EtOH seeking, consumption, and an insensitivity to outcome devaluation, the latter indicative of habitual EtOH seeking. We also found altered consummatory lick patterns in CIE-exposed mice compared to Air controls. While CIE mice had significantly more licks in a burst and a longer burst duration, there were no differences in the total number of bursts compared to Air controls. Furthermore, these EtOH consummatory behaviors correlated with blood EtOH concentrations (BECs), while EtOH-seeking responses did not.Conclusions: Our results confirm that EtOH dependence can produce habitual EtOH seeking and suggests the increased EtOH consummatory behaviors following EtOH dependence are separable from decision-making processes controlling EtOH seeking.

Selective Deficits in Contingency‐Driven Ethanol Seeking Following Chronic Ethanol Exposure in Male Mice

“…In contrast to recent findings reporting significant escalation in ethanol consummatory behavior (i.e., licking) following CIE (Renteria et al, 2020), we did not observe an escalation in licking following CIE (data not shown). A mixed‐model ANOVA indicated no significant CIE × session interaction, F (12, 176) = 0.9448, p = 0.5037.…”

“…Importantly, this indicates that the Air control mice may have developed contingency‐insensitive habits following repeated training on these schedules, but that CIE facilitated the transition from actions to habits. This interpretation is complementary to findings from others that CIE induces outcome devaluation‐insensitive ethanol‐seeking behaviors (Renteria et al, 2020), indicating that a history of chronic ethanol exposure may facilitate habitual behaviors that are both outcome and contingency‐insensitive. This is further consistent with reports that ethanol‐seeking habits develop more rapidly than sucrose‐seeking habits (Dickinson et al, 2002).…”

“…Individuals with alcohol use disorders show an overreliance on habitual response strategies (Sjoerds et al, 2013), though it is not clear whether this aberrant habit formation is a result of chronic alcohol use or may have been a predisposing factor to the development of alcoholism. While individual differences in corticolimbic striatal circuitry that regulates flexible reward‐seeking behavior have been identified to predict the development of addiction‐related behaviors, including habitual ethanol seeking (Barker and Taylor, 2014; Barker et al, 2014), others observe that chronic intermittent ethanol exposure by vapor inhalation results in the development of habitual ethanol‐seeking behaviors that are resistant to devaluation (Barker et al, 2017; Renteria et al, 2020). These findings suggest that while propensity toward habit formation may contribute to the development of inflexible ethanol use, ethanol exposure itself can act directly to promote the loss of cognitive control over actions that characterizes AUDs.…”

“…To date, the preponderance of the research investigating ethanol‐seeking habits has focused on ethanol‐induced deficits in sensitivity to change in value through the use of outcome devaluation paradigms (Barker et al, 2010; Corbit et al, 2012; Dickinson et al, 2002; Renteria et al, 2020; Serlin and Torregrossa, 2014). In a majority of studies where contingency degradation and outcome value are assessed, loss of sensitivity to change in contingency and value appears to occur in parallel for both ethanol and nondrug rewards (e.g., Barker et al, 2014, 2017b, 2017c; Gourley et al, 2016).…”

“…Ethanol habits are known to develop more rapidly than sucrose‐seeking habits (Dickinson et al, 2002), but data suggest that ethanol exposure can promote the development of sucrose‐seeking habits as well (Corbit et al, 2012; Renteria et al, 2018a), suggesting that ethanol acts to dysregulate shared circuitry to promote habitual behavior. Based on findings that chronic intermittent ethanol (CIE) exposure by vapor inhalation resulted in insensitivity to outcome devaluation in ethanol seeking (Renteria et al, 2020) and that either voluntary ethanol self‐administration (Corbit et al, 2012) or CIE exposure (Renteria et al, 2018a) facilitated loss of sensitivity to outcome value in sucrose‐seeking behavior, we investigated the hypothesis that CIE would impair use of contingencies to guide sucrose and ethanol‐seeking behavior.…”