Histamine regulates release of neurotransmitters such as dopamine, serotonin, gamma-aminobutyric
acid (GABA), glutamate and also is involved in several functions in central nervous system (CNS). It has
been shown that histamine participates in disorders like seizure. It has been well documented that
morphine dose-dependently induces anti or proconvulsant effects. In the current study, we firstly
showed that morphine (1 mg/kg) exerts anticonvulsant effects which significantly reversed by naltrexone
administration. Secondly, we determined seizure threshold for H1 and H3 receptors agonists and
antagonists in mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. Our results showed that
activation of H1 receptors by 2-(2-Pyridyl)-ethylamine exerts anticonvulsant properties while inhibition
of H1 receptors by pyrilamine maleate induced proconvulsant effects. Furthermore, we showed that
immepip dihydrobromide, a H3 receptor agonist, increased seizure susceptibility to PTZ whereas thioperamide,
a H3 receptor antagonist increased seizure threshold. We also revealed that pretreatment with
morphine potently reversed the effects of histaminergic system on seizure threshold suggesting the
involvement of opioid system in alteration of seizure threshold by histaminergic drug
