Mechanism of imipramine-induced seizures in amygdala-kindled rats

The present study was undertaken to get insight in the possible mechanisms of imipramine-induced seizures in amygdala-kindled rats. The intraperitoneal (i.p.) injection of imipramine produced potent behavioral and electroencephalogram (EEG) seizures in amygdala-kindled rats. Histidine (1500 mg/kg, i.p.) and histamine (10 and 20 microg, i.c.v.) significantly attenuated the seizures induced by imipramine (50 mg/kg, i.p.) in kindled rats. In addition, the inhibition of imipramine-induced seizures by histamine (20 microg, i.c.v.) was antagonized by an H1 antagonist, pyrilamine. An H3 antagonist, thioperamide (50 microg, i.c.v.), also significantly attenuated the imipramine-induced seizures in kindled rats. The i.p. injection of alpha-methyl-p-tyrosine at a dose of 250 mg/kg significantly diminished the seizures induced by imipramine. However, p-chlorophenylalanine and physostigmine did not affect the imipramine-induced seizures to any extent. These data give strong hints that the H1 receptor antagonistic properties and the brain noradrenaline activating effects of imipramine are centrally involved in imipramine-induced seizures, and central serotonergic and cholinergic neurotransmissions are not involved in the seizures induced by imipramine in amygdala-kindled rats.