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. 2014 Dec;39(13):2919-27.
doi: 10.1038/npp.2014.151. Epub 2014 Jun 20.

Exaggerated Waiting Impulsivity Associated With Human Binge Drinking, and High Alcohol Consumption in Mice

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Free PMC article

Exaggerated Waiting Impulsivity Associated With Human Binge Drinking, and High Alcohol Consumption in Mice

Sandra Sanchez-Roige et al. Neuropsychopharmacology. .
Free PMC article

Abstract

There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18-25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.

Figures

Figure 1
Figure 1
(A) Participants were comfortably seated in front of a touch screen. Viewing distance was approximately 30 cm with a vertical visual angle of −30° and a horizontal visual angle of 0°. The task consisted of five independently moving blue circles (stimulus) represented in a ‘circular' motion in a tactile screen. We adopted moving targets in an attempt to increase attentional load, which, in the mouse task, comes about because reinforcer retrieval, as well as spontaneous locomotor activity diverts attention from the five-choice array. Below the stimuli and at the bottom of the screen, a home button was located. Trial commenced by the illumination of the house button (B). The participant was required to tap and hold onto the home button, and withhold responding until the stimulus presentation. After a designated inter-trial interval (ITI; s), one of the five circular visual stimuli modified its contour (D) and the participant was then required to tap into the highlighted circle and return to the home button. Illumination of the home button signaled the start of a new trial (E). Omissions (failure to respond to the signaled stimulus within a concrete period of time), incorrect responses (tapping into a non-designated circle), and premature responses (responses into the circles during the inter-trial interval before the stimulus presentation) were followed by a designated time-out period of 5 s (C). Perseverative responses (responding repeatedly to the circles after a correct detection) were also assessed. Total number of trials completed was determined, providing a measure of motivation. Following practice trials (correctly responding in each of the five signaled stimuli, or after 3 min, whichever came first), participants performed four task variants: a fITI and vITI session under simple task conditions (n=31–32; panel a); and a fITI and vITI session in combination with a dual task (n=44; panel b). During the dual task, participants were required to discriminate between sequences of low- and high-pitched tones (13 blocks of 10 trials; 1 high tone/block, presented in random order) and respond to the latter by pressing a space bar located in an external keyboard whilst performing the Sx-5CSRTT with their dominant index finger.
Figure 2
Figure 2
Sx-5CSRTT performance during a fixed ITI (fITI) and vITI sessions under simple task (top panels) and dual-task (bottom panels) conditions for NBD and BD. Mean (±SEM) of the percentage of (a, d) accuracy of responding, (b, e) percentage of omissions, and (c, f) premature responses. *p<0.05, **p<0.01 compared with NBD (independent sample t-test or non-parametric Mann–Whitney U-test).
Figure 3
Figure 3
Performance during the Two-Choice Impulsivity paradigm. Mean ±SEM of (a) proportion of immediate choices and (b) maximum number of consecutive delayed choices. *p<0.05 compared with NBD (independent sample t-test), (*) p=0.064.
Figure 4
Figure 4
Premature responding (mean±SEM) of C57BL/6J (B6, black bars/lines) and DBA2/J (D2, gray bars/lines) in the 5CSRTT during a (a) fITI (last session in stage 6) and vITI sessions, and across the different ITIs during the vITI session for mice (b) and human participants (c). *p<0.05 (independent t-test).

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