title: Protective effects of lithium chloride on seizure susceptibility: Involvement of α2-adrenoceptor.
abstract: For more than 60years, lithium has been the mainstay in the treatment of mental disorders as a mood stabilizer. In addition to the antimanic and antidepressant responses, lithium also shows some anticonvulsant properties. In spite of the ascertained neuroprotective effects of this alkali metal, the underlying mechanisms through which lithium regulates behavior are still poorly understood. Among different targets, some authors suggest neuromodulatory effects of lithium are the consequences of interaction of this agent with the brain neurotransmitters including adrenergic system. In order to study the involvement of α2-adrenergic system in anticonvulsant effect of lithium, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice. Injection of a single effective dose of lithium chloride (30mg/kg, i.p.) significantly increased the seizure threshold (p<0.01). The anticonvulsant effect of an effective dose of lithium was prevented by pre-treatment with low and per se non-effective dose of clonidine [α2-adrenoceptor agonist] (0.05, 0.1 and 0.25mg/kg). On the other hand, yohimbine [α2-adrenoceptor antagonist] augmented the anticonvulsant effect of sub-effective dose of lithium (10mg/kgi.p.) at relatively low doses (0.1, 0.5, 1 and 2.5mg/kg). Moreover, UK14304 [a potent and selective α2-adrenoceptor agonist] (0.05 and 0.1mg/kg) and RX821008 [a potent and selective α2D-adrenoceptor antagonist] (0.05, 0.1 and 0.25mg/kg) repeated the same results confirming that these modulatory effects are conducted specifically through the α2D-adrenoceptors. In summary, our findings demonstrated that α2-adrenoceptor pathway could be involved in the anticonvulsant properties of lithium chloride in the model of chemically induced clonic seizure.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.affiliation: Institut universitaire en santé mentale de Québec, Québec City, Québec, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Bahremand
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Ebrahimi
authors.affiliation: Motor Neuron Center, College of Physicians and Surgeons, Columbia University Medical Center, NY, USA.
authors.forename: Sara Ebrahimi
authors.initials: SE
authors.lastname: Nasrabady
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Taraneh
authors.initials: T
authors.lastname: Bahremand
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran" to the Ahmad reza Dehpour. Electronic address: dehpour@yahoo.com.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D000068438:Brimonidine Tartrate / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D018021:Lithium Chloride / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C000605312:2-(4-chloro-2,3-dihydrobenzofuran-2-yl)-4,5-dihydro-1H-imidazole; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D001572:Benzofurans; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D018021:Lithium Chloride; D003000:Clonidine; D010433:Pentylenetetrazole
keywords: Clonic seizure threshold; Clonidine; Epilepsy; Lithium chloride; Mice; α(2)-Adrenoceptor