Christina L Ruby, Laura N Marinos, Catherine F Zisk, Jiawen Zhang, Kaitlyn N Palmer, David J Bunion, Jacob D Dietzel and Natalie M Verbanes
It is common among American youth to mix alcohol (ethanol) with caffeine, which is associated with high dose/ high frequency drinking patterns and much greater health risks than alcohol alone. However, few studies to date have investigated the neurobiology of drugs used in combination. Growing evidence suggests that disruption of circadian (daily, 24 h) rhythms is key to the pathophysiology of addiction, yet the underlying mechanisms are poorly understood. Several key determinants of vulnerability to alcohol addiction, such as sensitivity to intoxication, reward responsiveness, and even drinking itself, vary diurnally. Here, we investigated the effect of caffeine on ethanolinduced ataxia in mice at six 4 h intervals over the 24 h photocycle. We observed a distinct diurnal variation in ataxia caused by ethanol (1.5 g/kg), with a nadir in sensitivity occurring early in the daytime (rest-phase). Co-administration of caffeine (7.5 mg/kg) advanced this diurnal pattern and surprisingly, abolished the nadir (e.g. increased sensitivity to ethanol early in the day). Our data support the notion that there may be a circadian rhythm in ethanol-induced motor incoordination and demonstrate that the effect of caffeine on this measure is dependent upon the time of day the two drugs are administered.