BETAHISTINE PREVENTS MEMORY LOSS IN PENTYLENETETRAZOLE-KINDLED MICE: THE ROLE OF ACETYLCHOLINESTERASE AND GLYCOGEN SYNTHASE KINASE-3β INHIBITION

Abdelsameea, Ahmed Ahmed; Mahmoud, Shireen Sami; Elsisi, Hossam A.

doi:10.21608/zumj.2022.167808.2660

BETAHISTINE PREVENTS MEMORY LOSS IN PENTYLENETETRAZOLE-KINDLED MICE: THE ROLE OF ACETYLCHOLINESTERASE AND GLYCOGEN SYNTHASE KINASE-3β INHIBITION

Document Type : Original Article

Authors

¹ Assistant professor of pharmacology, clinical pharmacology Department, Zagazig University, Zagazig, Egypt, E-mail:ahmedma_72@yaho.com

² Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

³ 2Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, Saudi Arabia. 2Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.

10.21608/zumj.2022.167808.2660

Abstract

Background: Recurrent seizures are usually associated with memory deficits. Objectives: This study assessed the effect of betahistine, histamine (H3) receptor antagonist, on memory deficits in pentylenetetrazole (PTZ)-kindled mice. Methods: 24 mice were allocated into saline, PTZ, and betahistine 5 mg-PTZ and betahistine 10 mg-PTZ equal groups. PTZ, 40mg/kg, was injected i.p. on alternate days while betahistine, 5 and 10 mg/kg doses, were i.p. injected once daily till 19th day. Seizure score was recorded after each PTZ injection. Finally, Y-maze and elevated plus maze tests were done then mice were sacrificed followed by brain excision for assessment of histamine, acetylcholine (Ach), acetylcholinesterase (AchE), phosphorylated glycogen synthase kinase-3βS9 (pGSK-3βS9) and phosphorylated Akt (p-Akt) levels. Results: In PTZ group, maximum seizure score was approached with decreased time spent and number of entries in the novel arm of Y-maze as well as increased transfer latency in the elevated plus maze. Histamine, Ach, pGSK-3βS9 and p-Akt were decreased with increased AchE level. Betahistine treatments decreased seizure score with increments in time spent and number of entries in the novel arm of Y-maze and decreased transfer latency in elevated plus maze in dose dependant manner. The drug increased histamine, Ach, pGSK-3βS9 and p-Akt levels while decreased AchE activity. Conclusion: Betahistine prevented PTZ-induced memory loss; an effect could be in part attributed to the enhanced cholinergic activity and GSK3-β inhibition.

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