Betahistine, prevents kindling, ameliorates the behavioral comorbidities and neurodegeneration induced by pentylenetetrazole

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A seizure may occur because of the imbalance between glutamate and gamma-aminobutyric acid (GABA). Recurrent seizures induce some cognitive problems, such as, depression, learning and memory deficits, and neurodegeneration. Histamine is an appropriate therapeutic target for epilepsy via its effect on regulating neurotransmitter release. Also, evidence indicates the effect of histamine on neuroprotection and alleviating cognitive disorders. An ideal antiepileptic drug is a substance, which has both anticonvulsant effects and decreases the comorbidities that are induced by repeated seizures. Betahistine dihydrochloride (betahistine) is a structural analog of histamine. It acts as histamine H1 receptor agonist and H3 receptor antagonist, which enhances histaminergic neuronal activities. In the present study, we examined the effect of betahistine administration on seizure scores, memory deficits, depression, and neuronal loss induced by pentylenetetrazole (PTZ). Eight- to ten-week-old BALB/c male mice (20–25 g) received betahistine, 1, and 10 mg/kg daily from 7 days before the onset of PTZ-induced kindling until the end of the establishment of the kindling. We found that betahistine prevented generalized tonic–clonic seizures induction and diminished forelimb clonic seizures intensity. Also, it decreased cell death in the hippocampus and cortex, ameliorated the memory deficit and depression induced by PTZ in the kindled animals. Altogether, these results indicate that pretreatment and repetitive administration with betahistine exerts antiepileptogenic and anticonvulsant activity. These findings might be due to the neuroprotective impact of betahistine in the hippocampus and cortex.