Dose-dependent Modulation of Pentylenetetrazol-induced Seizure Activity by Histamine and Receptor Antagonists in Wistar Rats

Background: Epileptic activity often involves key brain structures, like the hippocampus and amygdala, while histamine plays a crucial role in regulating neuronal excitability. Objectives: The primary objective of this research was to investigate how different doses of histamine influence seizure frequency and the potential therapeutic effects of histamine in conjunction with chlorpheniramine and ranitidine. Methods: Forty-eight Wistar rats (۲۸۰–۳۲۰ g) were divided into several groups, including control, histamine (۲, ۴, and ۸ µg/kg), chlorpheniramine, ranitidine, and combinations of histamine with these drugs. The rats were anesthetized with ketamine-xylazine (۷۰–۷ mg/kg), and precise injections of ۰.۵ µL of each drug were delivered into the amygdala using a Hamilton syringe. Brain activity was recorded before and after administering pentylenetetrazol (PTZ) (۸۰ mg/kg, i.p.) to induce seizures, followed by monitoring convulsive activity. Diazepam (۱۰ mg/kg, i.p.) was then given to suppress the seizures. Results: Histamine significantly reduced seizure frequency in a dose-dependent manner, and chlorpheniramine and ranitidine exhibited similar effects, both alone and in combination with histamine. Notably, although seizure frequency varied among groups, the amplitude of convulsive activity remained unchanged. Conclusion: The findings provide deeper insight into the role of histamine in seizure modulation and suggest potential therapeutic implications for epilepsy treatment.

کلیدواژه ها:

Neurotransmitter ، histamine ، Hippocampus ، Amygdala ، Epilepsy