“Drinking in the dark” (DID) procedures: A model of binge-like ethanol drinking in non-dependent mice

Abstract

This review provides an overview of an animal model of binge-like ethanol drinking that has come to be called “drinking in the dark” (DID), a procedure that promotes high levels of ethanol drinking and pharmacologically relevant blood ethanol concentrations (BECs) in ethanol-preferring strains of mice. Originally described by Rhodes et al. (2005), the most common variation of the DID procedure, using singly housed mice, involves replacing the water bottle with a bottle containing 20% ethanol for 2 to 4 hours, beginning 3 hours into the dark cycle. Using this procedure, high ethanol drinking strains of mice (e.g., C57BL/6J) typically consume enough ethanol to achieve BECs greater than 100 mg/dL and to exhibit behavioral evidence of intoxication. This limited access procedure takes advantage of the time in the animal’s dark cycle in which the levels of ingestive behaviors are high, yet high ethanol intake does not appear to stem from caloric need. Mice have the choice of drinking or avoiding the ethanol solution, eliminating the stressful conditions that are inherent in other models of binge-like ethanol exposure in which ethanol is administered by the experimenter, and in some cases, potentially painful. The DID procedure is a high throughput approach that does not require extensive training or the inclusion of sweet compounds to motivate high levels of ethanol intake. The high throughput nature of the DID procedure makes it useful for rapid screening of pharmacological targets that are protective against binge-like drinking and for identifying strains of mice that exhibit binge-like drinking behavior. Additionally, the simplicity of DID procedures allows for easy integration into other paradigms, such as prenatal ethanol exposure and adolescent ethanol drinking. It is suggested that the DID model is a useful tool for studying the neurobiology and genetics underlying binge-like ethanol drinking, and may be useful for studying the transition to ethanol dependence.

Modelos animales de adicción a las drogas

“…Este acceso a la sustancia de abuso comienza dentro del ciclo de oscuridad para los animales (de ahí su nombre) y suele ser un período comprendido entre 2-4 horas, es decir, en forma de atracón, simulando al patrón de consumo de alcohol más común entre los adolescentes en fin de semana, el conocido "botellón". Utilizando dicho procedimiento, normalmente los animales pueden alcanzar altas concentraciones de etanol en sangre, por lo que es un modelo muy interesante para estudiar la adicción al alcohol (Thiele y Navarro, 2014).…”

Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli

“…We used a 4-day 'drinking-in-the-dark' (DID) procedure with the first cohort of mice, an animal model of binge-like ethanol drinking which promotes high levels of ethanol that are associated with blood ethanol concentrations (BECs) in excess of 80 mg/dl in a 2-4-h testing period (Rhodes et al, 2005;Thiele and Navarro, 2014). Procedural details for the DID procedure have recently been described elsewhere .…”

Do Orexins contribute to impulsivity-driven binge consumption of rewarding stimulus and transition to drug/food dependence?

“…Thiele and cols. have recently proposed that overlapping neurobiological systems may be involved in early and later stages of ethanol addiction (Lowery-Gionta et al, 2010;Thiele and Navarro, 2014). The hypothesis holds that some of the neurochemical systems having a key role in addictive stages might be recruited early in time during the first stages of the addiction cycle in non-dependent organisms showing binge-like consumption (Lowery-Gionta et al, 2010;Thiele and Navarro, 2014).…”

“…Second, consistent with a role for OX in impulsivity-like behaviors, the OXr1 antagonist SB-334867 peripherally administered regulated impulsive behavior under both baseline and cocaine-stimulated conditions in a dynorphin-sensitive manner in food-restricted rats, as measured by premature responses exhibited in the 5-choice serial reaction time task (5-CSRTT) (Muschamp et al, 2014). Third, recent studies have highlighted the role of OX system in binge-like consumption of rewarding stimulus (sucrose, saccharin and ethanol) in non-dependent animals (Alcaraz-Iborra et al, 2014;Anderson et al, 2014;Olney et al, 2015) as measured by the Drinking in the Dark (DID) paradigm, a wellestablished procedure to reproduce pre-dependent episodes of human binge consumption patterns in mice (Thiele and Navarro, 2014). Thus, the OXr1 antagonist SB-334867 reduced sucrose, saccharin (AlcarazIborra et al, 2014) and ethanol (Anderson et al, 2014;Olney et al, 2015) binge-like drinking when administered peripherally and ethanol binge-like drinking when centrally infused (Carvajal et al, 2015) in non-deprived mice.…”

“…have recently proposed that overlapping neurobiological systems may be involved in early and later stages of ethanol addiction (Lowery-Gionta et al, 2010;Thiele and Navarro, 2014). The hypothesis holds that some of the neurochemical systems having a key role in addictive stages might be recruited early in time during the first stages of the addiction cycle in non-dependent organisms showing binge-like consumption (Lowery-Gionta et al, 2010;Thiele and Navarro, 2014). Consistent with the idea, they have provided compelling evidence supporting the role of Corticotropin-Releasing Factor (CRF) (a peptide known to be involved in ethanol dependence) (Roberto et al, 2010) in ethanol binge-drinking in "non-dependent" animals (Lowery-Gionta et al, 2010).…”