Effects of endogenous histamine on seizure development of pentylenetetrazole-induced kindling in rats

This study was performed to investigate whether or not endogenous histamine can protect seizure development of pentylenetetrazole (PTZ)-induced kindling in rats. An intracerebroventricular (i.c.v.) injection with clobenpropit (5 and 10 μg), a representative H₃-antagonist, significantly prolonged the onset of kindling and inhibited the seizure stages in a dose-dependent manner. Its action was significantly reversed by both immepip (2 μg, i.c.v.), an H₃-agonist, and α-fluoromethylhistidine (α-FMH, 10 μg, i.c.v.), a selective histidine decarboxylase inhibitor. α-FMH (20 μg, i.c.v.) and pyrilamine (1 and 5 mg/kg i.p.), a classical H₁-antagonist, markedly augmented the severity of seizure development of PTZ-induced kindling. Therefore, these results indicate that brain endogenous histamine plays a certain protective role on seizure development of PTZ-induced kindling in rats, and that its protective roles are mediated by H₁-receptors.