Adenosine uptake inhibitors potentiate the sedative effects of adenosine

A major action of adenosine is the induction of profound behavioral inactivity. 6-(4-Nitrobenzyl)-thioinosine (NBI) and 6-(2-hydroxy-5-nitrobenzyl)-thioguanosine (NBG) have been shown to inhibit adenosine uptake. To investigate the possible synergism between exogenous ligand and reuptake inhibition, mice were treated with NBI or NBG + adenosine. NBI and NBG potentiated the effects of adenosine at doses which did not in themselves induce behavioral inactivity. These behavioral results support the proposed role of NBI and NBG as adenosine uptake site blockers which increase synaptic concentrations of adenosine and postsynaptic responses to adenosine in vivo.