INTERACTIONS BETWEEN ETHANOL, ENDOGENOUS ADENOSINE AND ADENOSINE UPTAKE IN HIPPOCAMPAL BRAIN-SLICES

Previous studies have suggested that ethanol (EtOH) can inhibit the tr ansport of adenosine (ADO) into cells, and that ADO may be an importan t mediator of the effects of EtOH in the brain. Nevertheless, there ha ve been few functional studies of EtOH-ADO interactions at the cellula r level in the brain that support this hypothesis. In the present stud y, the effects of EtOH were compared with those of other more well-cha racterized ADO uptake inhibitors, using evoked field excitatory postsy naptic potentials in the rat hippocampal slice preparation as a measur e of changes in extracellular ADO. As has been reported previously, th e ADO uptake inhibitor dipyridamole (DIPY) depresses the amplitude of field excitatory postsynaptic potentials responses in a dose-dependent , theophylline-reversible manner, suggesting that, by inhibiting ADO t ransport, DIPY significantly increases the concentration of extracellu lar ADO. Nitrobenzylthioinosine, which inhibits a different ADO transp orter that has been reported to be selectively affected by EtOH, had n o significant effect on its own, but produced a weak inhibitory effect when combined with DIPY. When tested alone, EtOH (20 and 100 mM) prod uced variable effects on the field excitatory postsynaptic potentials response, but overall did not have a statistically significant effect. Unlike nitrobenzylthioinosine, EtOH did not produce a significant dep ression of evoked responses when combined with DIPY. These experiments demonstrate that, although EtOH may inhibit the nitrobenzylthioinosin e-sensitive ADO transporter, intoxicating concentrations do not produc e large enough changes in extracellular ADO in hippocampal slices to b e detectable using electrophysiological response measures.