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 alteration in glucose utilization in the whole brain, as well as in the specific brain areas (cerebellum and brain stem), was investigated. Mice were 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. Ethanol (2 g/kg, ip) markedly increased the glucose utilization in whole brain 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. However, adenosine agonist N-6-cyclohexyladenosine (CHA; 0.1 mg/kg, ip) on the contrary, significantly accentuated ethanol-induced increase in glucose utilization in these tissues that was nearly completely blocked by theophylline pretreatment Theophylline alone did not produce any significant change in glucose utilization, whereas CHA alone (in vivo and in vitro) significantly increased glucose utilization, as well as ethanol-induced increase in glucose utilization in an additive manner. Relevant supportive data were obtained by experiments in which adenosine deaminase (ADA), p-sulfophenyltheophylline (8-SPT), and CHA were administered 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-induced increase in glucose utilization in an additive manner. Collectively, data seemed to suggest an adenosinergic modulation of ethanol-induced increase in glucose utilization in whole brain, as well as in the cerebellum and brain stem via specific adenosine receptors.