Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: influence of experimental and environmental factors.
It has been recently shown that the variable anticonvulsant effect of phenytoin in the kindling model is not a characteristic of all kindled rats. In a population of amygdala-kindled Wistar rats, subgroups can be selected which consistently respond to phenytoin with an increase in afterdischarge threshold (responders) or which never show such an increase (non-responders). This study examined retrospectively the influence of technical and environmental factors on the results of several prospectively performed phenytoin selections during the last few years. Male and female Wistar rats were implanted with bipolar electrodes aimed at the basolateral amygdala and subsequently kindled. The fully kindled rats were tested for their ability to consistently respond to phenytoin (75 mg/kg i.p.) with an increase of afterdischarge threshold in three consecutive trials. Analysis of 158 Wistar rats of both genders revealed no significant influence of either plasma concentration of phenytoin, kindling parameters, precise electrode location, or differences in focal histology on the result of phenytoin selection. Furthermore, the ability to respond to phenytoin was not associated with the season or the ambient atmospheric pressure during the selection procedure. The data suggest that the difference between phenytoin responders and non-responders is not due to experimental factors, but may rather be genetically determined.
Ebert
U
U
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany. uebert@pharma.tiho-hannover.de
Rundfeldt
C
C
Lehmann
H
H
Löscher
W
W
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001274:Atmospheric Pressure; D004056:Differential Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D004351:Drug Resistance; D004594:Electrophysiology; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D010672:Phenytoin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012621:Seasons
D000927:Anticonvulsants; D010672:Phenytoin