The most commonly used depressants and stimulants are various forms of ethanol and caffeine. Caffeine can be used in combination with ethanol to potentiate its stimulatory effect or to negate its sedative effect. The aim of this investigation was to examine the effects of the concurrent administration of caffeine and ethanol on hypnosis and motor coordination.

All experiments were performed in male Sprague-Dawley rats (250-300g). The effect of caffeine on ethanol-induced hypnosis was determined by measuring the duration of loss of the righting reflex. The animals were dosed p.o. with either vehicle or caffeine (2-100 mg/kg) 60 min prior to ethanol (2.5 g/kg) i.p. administration. Once sedated, animals were placed in the supine position on a heated pad, and the time taken for them to regain their righting reflex was recorded.

The effect of caffeine on ethanol-induced motor incoordination was measured using an accelerating rotarod (Harvard Apparatus Coordin8®). The animals were trained to remain for 30 s (accelerating at 0.6 r.p.m./s) two times per day starting two days before the test. On the day of testing the animals were randomised into groups and prior to drug administration they were tested on the rotarod to determine pre-dose fall time when accelerating at 1 r.p.m./s. The animals were then dosed with either vehicle, ethanol (2.5 g/kg) or ethanol (2.5 g/kg) + caffeine (2-100 mg/kg). All drugs were administered p.o. (dose volume 10 ml/kg). The animals were tested 60, 90, 120, 180 and 300 minutes post dose.

The results are expressed as the mean ± SEM of either the actual duration of the loss of righting reflex or the % pre-dose fall time. All data were evaluated by one-way ANOVA and a post hoc multiple comparison Newman-Keuls tests.Table 1: Effect of caffeine in ethanol (2.5g/kg) induced hypnosis and motor incoordination.

***p<0.001 vs Ethanol (2.5g/kg) + Vehicle, +++p<0.001 vs Caffeine (20mg/kg) + Ethanol, +p<0.05 vs Caffeine (20mg/kg) + Ethanol, #p<0.05 vs Vehicle, §p<0.05 vs Caffeine (20mg/kg) + Ethanol (2.5g/kg).

The results demonstrate a biphasic effect of caffeine in both ethanol induced hypnosis and motor coordination. At the lower concentrations tested caffeine significantly decreased the hypnotic effect of ethanol and inhibited the ethanol induced motor-incoordination, but this was reversed at the higher doses tested. Caffeine is likely to exert its effect on adenosine receptors (Yacoubi et al., 2000). Further studies are required with adenosine receptor subtype specific ligands to determine the mechanism of the biphasic effects noted in this study.

Yacoubi M.E.I., Ledent, C., Menard, J.F. et al. (2000), Br. J. Pharmacol. 129, 1465-1473.