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.
Ago
Jun
J
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Ishikawa
Takashi
T
Matsumoto
Naotaka
N
Ashequr Rahman
M
M
Kamei
Chiaki
C
D000679:Amygdala / Q000473:pathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004569:Electroencephalography; D007099:Imipramine / Q000633:toxicity*; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D009638:Norepinephrine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D003292:Convulsants; D007099:Imipramine; D009638:Norepinephrine