Determination of the threshold for convulsions by direct cortical stimulation

In this study we investigated whether determination of the convulsion threshold by electrical stimulation of the cortex could be used as a simple test for measuring anticonvulsant drug activity in unrestrained, unanaesthetized rats. Pulse trains delivered to electrodes implanted in the frontoparietal cortex elicited convulsions, similar to those seen in the classical electroshock tests. The threshold could be determined rapidly with pulse trains which increased in strength in a ramp-shaped fashion (bipolar pulses of 2 msec, 50 pulses/sec, increment 1.3 microA/pulse). The threshold was defined as the current needed to elicit forelimb clonus. Upon repeated stimulation the threshold declined from a value of about 600 microA to about 350 microA in 20 sessions. Thereafter, continued testing did not result in considerable changes in threshold. After stabilization, the convulsion threshold could be determined repeatedly with intervals as short as 5 min. Following i.p. injection of 5 mg/kg of diazepam an elevation of the threshold of 30% was observed 0.5 h after injection. After 5 daily injections, evidence for the development of complete tolerance was obtained. After i.v. injection of 8 mg/kg oxazepam, the threshold increase reached a peak level of 75% after 20 min. The changes in threshold followed arterial blood concentration of oxazepam, which was maximally 4.8 micrograms/ml immediately after injection. The threshold returned to baseline in approximately 6 h. The results of the present study show that with our procedure anticonvulsant drug activity can be accurately, rapidly and repeatedly determined in individual animals, both in acute and chronic experiments.