Development of Amygdaloid Kindling in Histidine Decarboxylase–deficient and Histamine H1 Receptor–deficient Mice.

Purpose: 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. [ABSTRACT FROM AUTHOR]