Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade

Abstract : The role of the adenosine A(2A) receptor in the hypnotic effects of ethanol was assessed in mice. The duration of the loss of righting reflex following acute ethanol administration was shorter for A(2A) receptor-deficient mice (A(2A)R KO) than for wild-type mice (A(2A)R WT), whereas the fall in body temperature was not different between the two phenotypes. In contrast, the duration of the loss of righting reflex was increased in A(2A)R KO mice versus controls after administration of pentobarbital. Dipyridamole, an inhibitor of adenosine uptake, increased the sleep time observed following administration of ethanol in CD1 mice and in A(2A)R WT but not in A(2A)R KO mice. SCH 58261, a selective A(2A) receptor antagonist, unlike DPCPX, a selective A(1) receptor antagonist, shortened the duration of the loss of righting reflex induced by ethanol, thus mimicking the lack of receptor in deficient mice. Finally, the non-selective adenosine receptor antagonist caffeine (25 mg/kg) reduced ethanol-induced hypnotic effects. These results indicate that the activation of A(2A) receptors that follows an increase in extracellular adenosine levels caused by the administration of high doses of ethanol plays a role in its hypnotic effects. Thus, A(2A) receptor antagonists may be useful therapeutic agents for alleviating ethylic coma.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02187011
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Soumis le : mercredi 17 juillet 2019 - 15:30:59
Dernière modification le : vendredi 19 juillet 2019 - 10:24:06

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M El Yacoubi, C Ledent, M Parmentier, J Costentin, J-M Vaugeois. Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade. Neuropharmacology, 2003, 45 (7), pp.977-85. ⟨10.1016/S0028-3908(03)00254-5⟩. ⟨hal-02187011⟩

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