Development of amygdaloid kindling in histidine decarboxylase-deficient and histamine H1 receptor-deficient mice.
OBJECTIVE
This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)-deficient and histamine H1 receptor (H1R)-deficient mice.


METHODS
Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant-current stimulator and continued until a generalized convulsion was obtained.


RESULTS
The development of amygdaloid kindling in HDC-deficient and H1R-deficient mice was significantly accelerated compared with that in their respective wild-type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC-deficient and H1R-deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild-type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R-deficient mice at the same dose.


CONCLUSIONS
These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling.
Hirai
Tadashi
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Okuma
Chihiro
C
Harada
Chie
C
Mio
Mitsunobu
M
Ohtsu
Hiroshi
H
Watanabe
Takeshi
T
Kamei
Chiaki
C
D000679:Amygdala / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006639:Histidine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000172:deficiency* / Q000235:genetics; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011969:Receptors, Histamine H1 / Q000172:deficiency* / Q000235:genetics
D011969:Receptors, Histamine H1; D006639:Histidine; D006640:Histidine Decarboxylase