Abstract
Deficits in executive control have frequently been associated with alcohol use disorder. Here we investigated to what extent pre-existing genetically encoded levels of impulsive/inattentive behavior associate with motivation to take alcohol and vulnerability to cue-induced reinstatement of alcohol seeking in an operant self-administration paradigm. We took advantage of BXD16, a recombinant inbred strain previously shown to have enhanced impulsivity and poor attentional control. We compared BXD16 with C57BL/6J mice in a simple choice reaction time task (SCRTT) and confirmed its impulsive/inattentive phenotype. BXD16 mice were less active in a novel open field (OF), and were equally active in an automated home cage environment, showing that increased impulsive responding of BXD16 mice could not be explained by enhanced general activity compared to C57BL/6J mice. After training in a sucrose/alcohol fading self-administration procedure, BXD16 showed increased motivation to earn 10% alcohol solution, both under fixed ratio (FR1) and progressive ratio (PR2) schedules of reinforcement. Responding on the active lever readily decreased during extinction training with no apparent differences between strains. However, upon re-exposure to alcohol-associated cues, alcohol seeking was reinstated to a larger extent in BXD16 than in C57BL/6J mice. Although further studies are needed to determine whether impulsivity/inattention and alcohol seeking depend on common or separate genetic loci, these data show that in mice enhanced impulsivity coincides with increased motivation to take alcohol, as well as relapse vulnerability.
Highlights
Deficits in executive functions, such as enhanced impulsivity and poor attentional control, have been associated with substance use disorders (Bickel et al, 2012), including that of alcohol (Verdejo-Garcia et al, 2008)
We recently showed that the same BXD16 strain was among the three poorest performing strains in a panel of 41 other BXD strains with respect to attentional performance in a 5-choice serial reaction time task (5CSRTT)
simple choice reaction time task (SCRTT) BXD16 mice were more impulsive in terms of percentage of premature Go-responses during presentation of the start stimulus compared with C57BL/6J mice (Figure 1A; strain: F(1,17) = 6.87, P < 0.05)
Summary
Deficits in executive functions, such as enhanced impulsivity and poor attentional control, have been associated with substance use disorders (Bickel et al, 2012), including that of alcohol (alcohol use disorder) (Verdejo-Garcia et al, 2008). We recently showed that the same BXD16 strain was among the three poorest performing strains in a panel of 41 other BXD strains with respect to attentional performance in a 5-choice serial reaction time task (5CSRTT). In this task mice are required to respond to a brief (1 s) light stimulus in one of five response apertures. BXD16 mice showed a high intra-individual variability in correct response latencies as well as low response
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