The effects of chronic desmethylimipramine on entorhinal cortical kindling in rats.

Chronic pretreatment of rats with desmethylimipramine (DMI) significantly slowed the rate of seizure generalization elicited by repeated electrical stimulation of the entorhinal cortex (kindling). An identical drug regimen administered to either fully kindled rats or rats partially kindled to early motor seizure stages failed to significantly alter kindling profiles in these animals. Under these latter conditions, in fact, there was a tendency for chronic DMI to exacerbate seizure activity. The effect of chronic DMI pretreatment to slow the development of kindled seizure generalization did not occur if a two-week delay was interposed between the end of drug treatment and the beginning of kindling trials. Results suggest that the retardation of entorhinal cortical kindling rate is dependent on DMI-induced CNS adaptations which recover within two weeks following treatment, and this effect is dependent on the presence of DMI-induced adaptations in a naive (unkindled) nervous system. Alterations of either the kindled state or the adaptational state produced by chronic drug eliminate the slowing of seizure generalization observed when both conditions are present.