Face validity of a pre‐clinical model of operant binge drinking: just a question of speed

Abstract

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.

Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain

“…In summary, preclinical evidence show that CBD may be of strong therapeutic interest in AUD and could have a significant action on drinking levels in human subjects with AUD, since it is effective on different aspects of the disease (intake, motivation, relapse, anxiety, and impulsivity). However, it should be noted that there are no available data on CBD efficacy in more relevant animal models of AUD, such as binge drinking models (Jeanblanc et al, 2018; Jeanblanc et al, 2019) or in models that use more chronic exposure to ethanol and behaviors linked to addiction (loss of control over intake, compulsive use of ethanol, increased motivation) (Meinhardt and Sommer, 2015). Thus, whether CBD is effective in animal models such as the postdependent state, in which rats drink ethanol for months and are exposed to ethanol vapors in order to induce dependence, is unknown.…”

Is R(+)‐Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side

“…The biological action of the racemic drug Baclofen is known to reside with the active R(+)‐Baclofen 27 . We have recently demonstrated that R(+)‐Baclofen reduced alcohol intake, motivation to consume alcohol and alcohol relapse in a relevant animal model of binge drinking 28‐30 . Altogether these data demonstrated that R(+)‐Baclofen is the most interesting enantiomer; however, the data have been obtained in inbred mice and selectively bred mice and rats and no study compared the effect of R(+)‐Baclofen to those of RS(±)‐Baclofen and no data are available regarding interindividual responses.…”

Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat

“…While animal models are critical for experimental control over factors such as diet and ethanol (EtOH) exposure patterns, pharmacologically relevant BALs can be difficult to achieve (Li et al, 1979, but see Fabio et al, 2014; Jeanblanc et al, 2018). “Dependence,” objectively defined by the presence of withdrawal signs, has be induced with high doses of EtOH, typically via intragastric (French, 2001), intraperitoneal (Pascual et al, 2009, 2014), or vapor (Roberts et al, 2000; Vendruscolo and Roberts, 2014) exposure.…”