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Mechanism of the Inhibitory Effect of Histamine on Amygdaloid‐Kindled Seizures in Rats

2001; Wiley; Volume: 42; Issue: 12 Linguagem: Inglês

10.1046/j.1528-1157.2001.05601.x

1528-1167

Chihiro Okuma, Tadashi Hirai, Chiaki Kamei,

Amino Acid Enzymes and Metabolism

Summary: Purpose: The mechanism of the inhibitory effect of histamine on amygdaloid‐kindled seizures was investigated in rats. Methods: Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. A guide cannula made of stainless steel tubing was implanted into the right lateral ventricle. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. EEG was recorded with an electroencephalograph; stimulation of the amygdala was applied bipolarly every day by a constant‐current stimulator and continued until a generalized convulsion was obtained. Results: Intracerebroventricular (i.c.v.) injection of histamine at doses of 2–10 μg resulted in a dose‐related inhibition of amygdaloid‐kindled seizures. I.c.v. injection of calcium chloride at doses of 10–50 μg and A23187 at doses of 2–10 μg also caused dose‐dependent inhibition of amygdaloid‐kindled seizures. Calcium chloride at a dose of 10 μg, which showed no significant effect on amygdaloid‐kindled seizures when used alone, significantly potentiated the effect of histamine. Similar findings were observed with A23187 at a dose of 2 μg. In addition, EGTA and EGTA/AM antagonized the inhibition of kindled seizures induced by histamine. Moreover, the inhibition of kindled seizures induced by histamine was antagonized by KN62. However, calphostin C did not antagonize the inhibitory effect of histamine. Conclusions: These results indicated that histamine‐induced inhibition of amygdaloid‐kindled seizures may be closely associated with a calcium calmodulin‐dependent protein kinase II activation pathway.