Properties of the convulsive threshold determined by direct cortical stimulation in rats.
The threshold for convulsions in rats can be determined by applying ramp-shaped pulse trains directly to the cerebral cortex in rats, which provides a convenient model for investigating anticonvulsant drug effects. This study was undertaken to extend a previous study on the properties of this model. Analysis of the cortical EEG, recorded from two motor areas and one somatosensory area, showed that the start of clonic forepaw movement, marking the convulsive threshold, is preceded by the appearance of sharp negative spikes at the electrodes in the two motor areas. There was a strong linear relation between the clinically determined threshold and the EEG derived threshold (r = 0.93, slope 0.99, SD 0.04), confirming the validity of the clonic movement threshold as an objective and accurate measure. Examination of the seizure patterns seen with various degrees of suprathreshold stimulation led to the distinction between a threshold for localized and for generalized seizure activity (TLS and TGS respectively). Carbamazepine selectively and strongly increased the TGS, whereas it only slightly affected the TLS, indicating that cortical stimulation can be used to select drugs that specifically prevent seizure spread, for which carbamazepine is a prototype. It was found that the TLS was not affected by testing at intervals as short as 1 min, provided that no self-sustained seizures were induced. However, if the TGS was passed, the TLS was increased substantially for at least 10 min, while complete recovery could take several hours. The intensity of stimulation, rather than seizure duration, appeared to be the determinant for the TLS increase. There was no seasonal influence or effect of stimulation electrode depth. There may be a minor effect of experience in using the test. It was concluded that the observed variability was mainly an intrinsic property of the individual animal.
Voskuyl
R A
RA
Department of Physiology, University of Leiden, Netherlands.
Hoogerkamp
A
A
Danhof
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D004558:Electric Stimulation; D004566:Electrodes; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology*
D000927:Anticonvulsants