Development of PHT-PB-resistant amygdala-kindled rats and expression of MDR1

Objective: To study the method of development of PHT-PB-resistant amygdala-kindled rats. Methods: By examining the effects of the antiepileptic drags PHT and PB in a group of rapidly kindled rats, the 40 animals with different sensitivity to these drags were selected. Then using immunohistochemistry method to determinate the expression of PGP in the brain of the rats. Results: Using determination of the after discharge threshold for evaluation of PHT's and PB's anticonvulsant effects, 6 animals showed no increase in their ADT at repeated test trials with PHT or PB (from PHT-PB- resistant rats), and 6 animals exhibited reproducible increase in ADT about 100% after injection of PHT or PB (from PHT-PB-nonresistant rats). The immunohisto-chemistry for P-glycoprotein showed increased staining in capillary endothelium in the samples from PHT-PB-resistant rats as compared with staining in PHT-PB-nonresistant rats, in extensive fields of bilateral cerebral hemispheres (P < 0.05). Conclusion: The procedure, using PHT, PB to screening kindling models to make PHT-PB-resistant amygdala-kindled rats, would be reliable. Overexpression of PGP in PHT-PB-resistant rats would suggest that the kindled rats with PHT-PB resistance could serve as reliable models of drug resistant epilepsy. The kindled rats with PHT-PB resistance might be a resource for the investigation of the mechanisms for drug resistance in epilepsy.