ECS seizure threshold: normal variations, and kindling effects of subconvulsive stimuli.

Abstract

The efficacy and adverse effects of electroconvulsive therapy are generally believed to depend upon the extent to which an administered stimulus is suprathreshold. The seizure threshold is therefore an important biologic marker. We sought to examine the variability of the electroconvulsive shock (ECS) seizure threshold in rats, and to identify factors influencing the threshold, to guide future research using animal models. We administered once-daily subconvulsive stimuli to Wistar rats beginning at a charge of either 1 mC (n = 25) or 5 mC (n = 25) and titrated the dose upward in 1-mC steps until the baseline seizure threshold was identified. Two weeks later, we divided each group into two subgroups and administered stimuli that were either at or 2 mC below the baseline threshold, and titrated the dose upward, again in 1-mC steps once daily, until the final threshold was identified. The mean baseline seizure threshold was 3.8 mC when upward titration was begun at 1 mC, and 6.7 mC when upward titration was begun at 5 mC (p < 0.001). Two weeks later, titration from baseline-subthreshold stimuli was associated with a lower final threshold in the 5-mC group, while titration from baseline-threshold stimuli was associated with a higher final threshold in the 1-mC group (p < 0.006). The ECS seizure threshold ranged from 3 to 7 mC in this sample of rats; since the twofold variation is very small relative to clinical contexts, it is unlikely that ECS research needs to be threshold-based. The administration of low-dose, once-daily subconvulsive stimuli significantly lowered the seizure threshold; while this kindling effect wore off within 2 weeks, thresholds otherwise identified remained stable at the 2-week time point.