Chronic but not acute treatment with antidepressants enhances the electroconvulsive seizure response in rats

The effects of the chronic administration of antidepressants on threshold electroconvulsive (ECS) seizures were evaluated in rats. Initially, tonic-clonic seizures were induced in 90% of the animals. Of those animals responding with tonic-clonic seizures, 42% had hindlimb extension (extensors); the remainder showed only hindlimb flexion (flexors). No alteration in the pattern of seizures was observed 24 hr after a single oral dose of any of the antidepressant drugs. The rats were then treated with a total of 20 consecutive daily doses of antidepressants and threshold electroconvulsive seizure responses were evaluated 24 hr after the last dose. A significantly greater percentage of rats responded with extensor seizures after chronic treatment with amoxapine, chlorimipramine, parglyine and mianserin. There was no change in the pattern of seizures of the rats treated chronically with desipramine, but the duration of the clonic phase was reduced. After a 7 day period free of drugs a significantly greater percentage of animals had extensor seizures in the groups treated with amoxapine, chlorimipramine, pargyline and desipramine but not mianserin. In the light of evidence that chronic treatment with antidepressants reduces the activity of norepinephrine- or isoproterenol-sensitive adenylate-cyclase, and that the norepinephrine system is an important endogenous anticonvulsant factor in electroconvulsive seizures, these results suggest that the same mechanism may mediate both the therapeutic and proconvulsant effects of the chronic administration of antidepressants.