Protective effects of lithium chloride on seizure susceptibility: Involvement of α2-adrenoceptor

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 α 2 -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  2 -adrenoceptor agonist] (0.05, 0.1 and 0.25 mg/kg). On the other hand, yohimbine [α 2 -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 α 2 -adrenoceptor agonist] (0.05 and 0.1 mg/kg) and RX821008 [a potent and selective α 2D -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 α 2D -adrenoceptors. In summary, our findings demonstrated that α 2 -adrenoceptor pathway could be involved in the anticonvulsant properties of lithium chloride in the model of chemically induced clonic seizure.