Contingent Tolerance and Cross Tolerance to Anticonvulsant Effects in Amygdala-Kindled Seizures

A unique form of pharmacodynamic tolerance develops when effective anticonvulsants are given as pre-treatment before once-daily amygdala-kindled seizures in animals.1,2 This loss of efficacy (i.e., tolerance) is contingent upon the drug’s administration before, but not immediately after, the kindling stimulation.3, 4, 5, 6 This form of tolerance can be reversed after a period of seizures off anticonvulsants, or even continuing to give anticonvulsants on a once-daily basis but after a fully developed kindled seizure has already occurred.