Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior to major alterations in ionic homeostasis. It was found in vitro during ischemia that the rapidly formed adenosine, resulting from the intracellular breakdown of ATP, may inhibit synaptic transmission via the A₁ receptor subtype. The link between endogenous A₁ receptor activation during ischemia and the suppression of spontaneous electrocortical activity has not yet been established in the intact brain. The aim of this study was to investigate in vivo the effects of A₁ receptor antagonism by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) on the time to electrocortical suppression during global cerebral ischemia. Adult male Wistar rats under chloral hydrate anesthesia were subjected to 1 minute transient "four-vessel occlusion" ischemic episodes, separated by 20 minutes reperfusion. The rats were injected intraperitoneally with either 1.25 mg/Kg DPCPX dissolved in 2 ml/Kg dimethyl sulfoxide (DMSO) or the same volume of DMSO alone, 15 minutes before the third ischemic episode. Time to electrocortical suppression was estimated based on the decay of the root mean square of 2 channel electrocorticographic recordings. During the first 2 ischemic episodes electrocortical suppression appeared after ~ 12 seconds in both groups. After DMSO administration ischemic suppression remained unchanged. After DPCPX administration the time to electrocortical suppression was increased by ~ 10 seconds and bursts of activity were recorded during the entire ischemia. These effects disappeared within 15 hours after DPCPX administration. Our data provides evidence that during cerebral ischemia endogenous activation of A₁ receptors accelerates the electrical "shut-down" of the whole brain.