POSSIBLE CENTRAL ADENOSINERGIC MODULATION OF ETHANOL-INDUCED ALTERATIONS IN [C-14] GLUCOSE-UTILIZATION IN MICE

The possible role of brain adenosine in acute ethanol-induced alterati on in glucose utilization in the whole brain, as well as in the specif ic brain areas (cerebellum and brain stem), was investigated. Mice wer e killed 20-min postethanol, and the fresh tissue slices (300 mu m) of brain and/or specific brain areas were incubated for 100 min in a 5.5 mM glucose medium in Warburg flasks using [6-C-14]glucose as a tracer . Trapped (CO2)-C-14 was counted to estimate glucose utilization. Etha nol (2 g/kg, ip) markedly increased the glucose utilization in whole b rain and in both motor areas of brain. Theophylline (50 mg/kg, ip), an adenosine antagonist, significantly reduced ethanol-induced increase in glucose utilization in whole brain, as well as in brain areas. Howe ver, adenosine agonist N-6-cyclohexyladenosine (CHA; 0.1 mg/kg, ip) on the contrary, significantly accentuated ethanol-induced increase in g lucose utilization in these tissues that was nearly completely blocked by theophylline pretreatment Theophylline alone did not produce any s ignificant change in glucose utilization, whereas CHA alone (in vivo a nd in vitro) significantly increased glucose utilization, as well as e thanol-induced increase in glucose utilization in an additive manner. Relevant supportive data were obtained by experiments in which adenosi ne deaminase (ADA), p-sulfophenyltheophylline (8-SPT), and CHA were ad ministered in vitro to the slice preparations. Both ADA and 8-SPT were effective in almost completely blocking the ethanol-induced increase in glucose utilization, whereas CHA further enhanced the ethanol-induc ed increase in glucose utilization in an additive manner. Collectively , data seemed to suggest an adenosinergic modulation of ethanol-induce d increase in glucose utilization in whole brain, as well as in the ce rebellum and brain stem via specific adenosine receptors.