Threshold of synaptically elicited cortical spreading depression: drug-induced changes in rats.

The role played by synaptic phenomena in the initiation of Leão's spreading depression (SD) was examined in 30 rats anaesthetized with pentobarbital. SD was elicited by a train of 8 electrical pulses (0.1-0.3 msec, 10 Hz) applied through bipolar electrodes to the exposed cortical surface. The slow potential waves of SD were recorded from the stimulated site and from a remote cortical area. Threshold stimulus intensity (40 V) was increased above 80 V when low frequency stimulation (0.3 Hz, 10 V) was applied through the same electrodes. SD penetration into the stimulated area was blocked with higher stimulus rates (3-10 Hz) and intensities (20 V). Systemic application of the pyrrolopyrimidine drug BE 58-271 decreased SD threshold from 40 V to 7 V and reduced also the intensity and frequency of stimulation inducing the SD blockade. Similar effects were obtained with local application of 2 microliters of 10(-3) M 4-amino-pyridine to the stimulated cortex. The SD threshold was reduced from 40 V to 5 V, probably by prolonged depolarization of axon terminals and increased output of transmitters. Estimation of SD threshold revealed a biphasic effect of locally applied penicillin: an initial threshold decrease which gradually changed with the development of regular interictal discharge into a threshold increase and eventual SD blockade. It is concluded that sudden synaptic activation of cerebral cortex elicits SD whereas prolonged continuous stimulation decreases SD susceptibility, probably by enhancing the K+ clearance.