Conditioned reinforcement and locomotor activating effects of caffeine and ethanol combinations in mice

Abstract

A growing trend among ethanol drinkers, especially young adults, is to combine caffeinated energy drinks with ethanol during a drinking episode. The primary active ingredient of these mixers is caffeine, which may significantly interact with ethanol. We tested the two hypotheses that caffeine would enhance ethanol-conditioned place preference and also enhance ethanol-stimulated locomotor activity. The interactive pharmacology of ethanol and caffeine was examined in C57BL/6J (B6) mice in a conditioned place preference procedure with 1.75 g/kg ethanol and 3 mg/kg caffeine. Additionally, we used B6 mice to evaluate ethanol/caffeine combinations on locomotor activity using 3 doses of ethanol (1.75, 2.5 and 3.25 g/kg) and 2 two doses of caffeine (3 and 15 mg/kg). Both ethanol and caffeine administered alone increased preference for the drug paired side, though the effect of caffeine was more modest than that of ethanol. The drug combination produced significant place preference itself, but this was not greater than that for ethanol alone. Additionally, the combination of caffeine and ethanol significantly increased locomotion compared to giving either drug alone. The effect was strongest with a stimulatory dose of ethanol (1.75 g/kg) and waned with increasing doses of ethanol. Thus, combinations of caffeine and ethanol had significant conditioned reinforcing and locomotor activating effects in mice.

Inhibition of urokinase plasminogen activator “uPA” activity alters ethanol consumption and conditioned place preference in mice

“…In the present study, systemic administration of 1.5 g/kg of ethanol during five conditioning sessions, using an unbiased paradigm, induced robust CPP. Our result is similar to previously reported studies that indicated that a moderate dose of ethanol (1.5–2 g/kg) produced a significant CPP in C57BL/6 mice 43–46. Our previous research revealed that the systemic administration of B428 impaired cocaine-induced CPP,21 suggesting that uPA inhibition can impair the capacity of environmental cues that are associated with psychostimulation to elicit approach behavior.…”

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

“…The choice of the ethanol dose for the repeated exposure procedure was influenced by earlier work showing that the oral gavage route of administration can achieve high blood ethanol levels (Griffin et al , 2009), but also that it would not completely impair locomotion. We chose to use 15 mg/kg caffeine based on previous work showing that administration of this dose would significantly increase locomotor activity (Hilbert et al , 2013; Kaplan et al , 1989). For the exposure procedure, drugs were administered by oral gavage twice per day (at 0730h and 1530h).…”

“…Previous work has shown that caffeine can increase ethanol drinking in rats (Kunin et al , 2000; Rezvani et al , 2013) and can promote significant ethanol-induced taste aversions (Kunin et al , 2001). Additionally, it has been reported that combinations of caffeine and ethanol, compared to either drug alone, increase locomotor activity after acute injection (Hilbert et al , 2013) or while consuming the drug mixtures in a drinking paradigm (Fritz et al , 2014). Some research has also incorporated energy drinks into animal models and shown that they can antagonize locomotor deficits with higher doses of ethanol (Ferreira et al , 2004) similar to administering only caffeine (Hilbert et al , 2013).…”

“…Additionally, it has been reported that combinations of caffeine and ethanol, compared to either drug alone, increase locomotor activity after acute injection (Hilbert et al , 2013) or while consuming the drug mixtures in a drinking paradigm (Fritz et al , 2014). Some research has also incorporated energy drinks into animal models and shown that they can antagonize locomotor deficits with higher doses of ethanol (Ferreira et al , 2004) similar to administering only caffeine (Hilbert et al , 2013). Further, when given acutely energy drinks combined ethanol can significantly enhance activity when there is a history of ethanol exposure (Ferreira et al , 2013).…”

“…less aversion and less ataxia) and we hypothesized that caffeine combined with ethanol might augment the development of tolerance in these procedures. Additionally, to extend our earlier work looking at the effects of acute administration of these drugs on locomotion (Hilbert et al , 2013), we measured locomotor activity in an open field after the first oral gavage and then again after repeated oral gavage. Following from our earlier work (Griffin et al , 2013; Griffin et al , 2010; Hilbert et al , 2013; McGovern et al , 2014), our general hypothesis was that caffeine would increase the stimulatory effects of ethanol when administered acutely and that these effects would increase with repeated exposure.…”