Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs

The effects of endogenously released adenosine on the excitability of hippocampal neurons were studied using the novel and highly selective adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Extra- and intracellular recordings performed in area CA1 and CA3 of the guinea pig hippocampal slice preparation revealed that a transient suppression of an inhibitory purinergic tonus by DPCPX leads to sustained interictal-like epileptiform activity arising in area CA3. Once induced, the spontaneous burst discharges were apparently irreversible within the observation period, even after prolonged washout (2–3h) in normal solution. In contrast, the hyperpolarizing action of exogenous adenosine, which was substantially reduced by DPCPX, recovered within 30–60 min of drug washout, indicating that DPCPX was not irreversibly bound to the A1-receptor