Ethanol induces maladaptive impulse control and decreased seeking behaviors in mice

Abstract

Waiting impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are vulnerable to alcohol abuse. However, it is not well understood whether chronic alcohol use increases the propensity for impulsive behavior. Here, we establish a novel experimental paradigm demonstrating that continuous binge-like ethanol exposure progressively leads to maladaptive impulsive behavior. To test waiting impulsivity, we employed the 5-choice serial reaction time task (5-CSRTT) in C57BL/6J male mice. We assessed premature responses in the fixed and variable intertrial interval (ITI) 5-CSRTT sessions. We further characterized our ethanol-induced impulsive mice using Open Field, y-maze, two-bottle choice, and an action-outcome task. Our results indicate that continuous binge-like ethanol exposure significantly increased premature responses when mice were tested in variable ITI sessions even during a prolonged abstinent period. Ethanol-induced impulsive mice exhibited anxiety-like behavior during chronic exposures. This behavior was also observed in a separate cohort that was subjected to 20 days of abstinence. Ethanol-treated mice were less motivated for a sucrose reward compared with air-exposed control mice, while also demonstrating reduced responding during action-outcome testing. Overall, ethanol-treated mice demonstrated increased impulsive behavior, but a reduced motivation for a sucrose reward. Although waiting impulsivity has been hypothesized to be a trait or risk factor for AUD, our findings indicate that maladaptive impulse control can also be potentiated or induced by continuous chronic ethanol exposure in mice.

Keywords: AUD; alcohol; impulsivity; motivation; operant.

Figure 1.

Continuous ethanol vapor treatments increase impulsive responding in mice. (a) Pre-treatment baseline testing for showing no differences in percent premature responses, (b) accuracy, (c) or omitted trials. (d) Variable ITI impulsivity testing revealed differences in percent premature responses, (e) accuracy, and (f) omitted trials. n=8–10/group. *p<0.05 for effect of treatment. All data are expressed as ± s.e.m.

Figure 2.

Ethanol-induced impulsivity remains during abstinence. (a) Pre-treatment baseline testing for percent premature trials, (b) accuracy, (c) and omitted trials. (d) mice showed differences in percent premature, (e) accuracy, and (f) omitted trials during impulsivity testing through treatment abstinence. *p<0.05 for effect of treatment. n= 9–12/group. All data are expressed as ± s.e.m.

Figure 3.

Fixed baseline impulsivity testing comparison to variable ITI impulsivity testing. 2s LD, 5s ITI performance shows no differences in (a) percent premature responses. (b) Overall accuracy and (c) omitted trials were significantly different between groups. (d) Percent premature responses of AE and EE mice during pre-treatment fixed 7s ITI and post-treatment variable ITI testing. (e) AE mice did not show differences in changes in impulsivity between fixed and variable testing. (f) However, EE mice showed a significant change in impulsiveness between the testing sessions. n=12–15/group. #p<0.05 for effect of treatment. *p<0.05 for effect within the group. All data are expressed as ± s.e.m.

Figure 4.

Action-outcome testing displays decreased sucrose seeking behaviors toward the sucrose reward. (a) Schematic describing experimental training timeline from 5-CSRTT to action-outcome task. (b) EE mice showed decreased nose-poking per min, (b) time spent in the trough, (d) lower discrimination ratio, and (e) higher latency to trough. Linear regression analysis showed significant correlation with the percent premature response rate in the 5-CSRTT in (f) average nose-pokes per min, (g) time spent in trough, (h) discrimination ratio, and (i) latency to trough. Devaluation testing revealed no differences within or between groups in (j) nose-poking behavior. (k) AE mice showed significantly less time spent in the trough during devalued testing, but no differences in EE performance. (l) Latency to trough did not differ within or between groups during devaluation testing. (m) AE mice displayed decreased latency to the trough when a tone was presented during devaluation testing, where EE mice did not display this difference. *p<0.05 for effect of treatment. All data are expressed as ± s.e.m.