Binge drinking (BD) is often defined as a large amount of alcohol consumed in a 'short' period of time or 'per occasion'. In clinical research, few researchers have included the notion of 'speed of drinking' in the definition of BD. Here, we aimed to describe a novel pre-clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long-Evans male rats, we induced BD by regularly decreasing the duration of ethanol self-administration from 1-hour to 15-minute sessions. We compared the behavioral consequences of BD with the behaviors of rats subjected to moderate drinking or heavy drinking (HD). We found that, despite high ethanol consumption levels (1.2 g/kg/15 minutes), the total amounts consumed were insufficient to differentiate HD from BD. However, consumption speed could distinguish between these groups. The motivation to consume was higher in BD than in HD rats. After BD, we observed alterations in locomotor coordination in rats that consumed greater than 0.8 g/kg, which was rarely observed in HD rats. Finally, chronic BD led to worse performance in a decision-making task, and as expected, we observed a lower stimulated dopaminergic release within nucleus accumbens slices in poor decision makers. Our BD model exhibited good face validity and can now provide animals voluntarily consuming very rapidly enough alcohol to achieve intoxication levels and thus allowing the study of the complex interaction between individual and environmental factors underlying BD behavior.

Transcranial direct current stimulation (tDCS) is an emerging noninvasive brain neuromodulation technique aimed at relieving symptoms associated with psychiatric disorders, including addiction. The goal of the present study was to better identify which phase of alcohol-related behavior (hedonic effect, behavioral sensitization, self-administration, or motivation to obtain the drug) might be modulated by repeated anodal tDCS over the frontal cortex (0.2 mA, 20 min, twice a day for 5 consecutive days), using female mice as a model. Our data showed that tDCS did not modulate the hedonic effects of ethanol as assessed by a conditioned place preference test (CPP) or the expression of ethanol-induced behavioral sensitization. Interestingly, tDCS robustly reduced reacquisition of ethanol consumption (50% decrease) following extinction of self-administration in an operant paradigm. Furthermore, tDCS significantly decreased motivation to drink ethanol on a progressive ratio schedule (30% decrease). Taken together, our results show a dissociation between the effects of tDCS on “liking” (hedonic aspect; no effect in the CPP) and “wanting” (motivation; decreased consumption on a progressive ratio schedule). Our tDCS procedure in rodents will allow us to better understand its mechanisms of action in order to accelerate its use as a complementary and innovative tool to help alcohol-dependent patients maintain abstinence or reduce ethanol intake.

Ethanol-induced behavioral sensitization (EIBS) is thought to play a key role in addiction. However, whether EIBS is linked to an increase in the motivation to selfadministerethanol in an operant paradigm has never been demonstrated, and thus, the motivational sensitization theory (increase in drug wanting) has not been yet confirmed. We investigated using the operant ethanol self-administrationparadigm if the motivation to self-administerethanol (breakpoint) is increased in female mice prone to develop EIBS. Outbred female Swiss mice were treated once a day with 2.5-g ethanol per kilogram during 10 days and challenged with the same dose of ethanol 7 days later. EIBS-pronegroup was characterized by a significant increase in locomotion between the challenge day and day 1. When the difference was not significant, mice were considered as the "EIBS-resistant"group. Mice were then trained to nose poke for a 20% ethanol solution reinforcer under a FR1 and then a FR-2schedule of reinforcement. Motivation was assessed more directly with a progressive ratio schedule. Our results show that there is a positive correlation between EIBS and both the level of intake and motivation. Interestingly, acquisition of ethanol self-administrationwas faster in sensitized mice that also display a quick and long-lastingincrease in ethanol intake together with a lack of effect of alcohol challenge on c-Fosexpression restricted to the dorsolateral striatum. These results further support that EIBS vulnerability is crucial in the development of addictive behaviors and suggest a potential link with habit learning processes.