Protective Effects of Lithium Chloride on Seizure Susceptibility: Involvement of Α2-Adrenoceptor Publisher Pubmed



Payandemehr B¹ ; Bahremand A² ; Ebrahimi A¹ ; Nasrabady SE³ ; Rahimian R¹ ; Bahremand T¹ ; Sharifzadeh M⁴ ; Dehpour AR^{1, 5} Show Affiliations
Source: Pharmacology Biochemistry and Behavior Published:2015

Abstract

For more than 60 years, 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 (30 mg/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 0.25 mg/kg). On the other hand, yohimbine [α2-adrenoceptor antagonist] augmented the anticonvulsant effect of sub-effective dose of lithium (10 mg/kg i.p.) at relatively low doses (0.1, 0.5, 1 and 2.5 mg/kg). Moreover, UK14304 [a potent and selective α2-adrenoceptor agonist] (0.05 and 0.1 mg/kg) and RX821008 [a potent and selective α2D-adrenoceptor antagonist] (0.05, 0.1 and 0.25 mg/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. © 2015 Elsevier Inc.