Mechanism of the inhibitory effect of histamine on amygdaloid-kindled seizures in rats.
OBJECTIVE
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 microg resulted in a dose-related inhibition of amygdaloid-kindled seizures. I.c.v. injection of calcium chloride at doses of 10-50 microg and A23187 at doses of 2-10 microg also caused dose-dependent inhibition of amygdaloid-kindled seizures. Calcium chloride at a dose of 10 microg, 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 microg. 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.
Okuma
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Hirai
T
T
Kamei
C
C
D000679:Amygdala / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D017871:Calcium-Calmodulin-Dependent Protein Kinases
D000001:Calcimycin; D002122:Calcium Chloride; D004533:Egtazic Acid; D006632:Histamine; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C046770:EGTA acetoxymethyl ester; C058819:calphostin C