Epilepsy is a disorder with high prevalence and severity. Although there are several anticonvulsant drugs available in the market, 30 to 40% of the patients are refractory to the treatment. Besides the seriousness of epilepsy per se, this disorder may be accompanied by many comorbidities such as depression, which is the main psychiatric comorbidity of epilepsy. The mechanisms involved in the relationship between epilepsy and depression are not clarified. Given that some anticonvulsant drugs can trigger or enhance depressive symptoms, while some antidepressant drugs can potentiate the severity of seizure, the concomitant treatments of both disorders can be problematic. On the other hand, some studies have shown that antidepressant drugs can be safe and even possess an anticonvulsant activity such as venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI). Considering that duloxetine, another SNRI, has a more potent inhibition of monoaminergic transporters and that there is no study about its influence on seizures, the aim of our study is to verify the potential anticonvulsant action of duloxetine against seizures induced by pentylenetetrazole (PTZ) on mice. With this aim, mice will be pre-treated with duloxetine (10, 20, 40 mg/kg/i.p.), and thirty minutes after, the animals will receive an intraperitoneal injection of PTZ (60 mg/kg, i.p.). In the following twenty minutes the animals are going to be evaluated. The threshold for the first myoclonic jerk, tonic-clonic seizure, the duration of seizures and survival will be quantified. The electroencephalographic analysis (EEG) was used to assess the severity of the seizures (wave’s amplitude increase). After this period the animals will be sacrificed, the cerebral cortex dissected and biochemical analysis (activity of superoxide dismutase (SOD), catalase (CAT), nitrite levels and lipid peroxidation) will be made to investigate the mechanisms by which this drug can influence seizures. The results exhibit the anticonvulsant action of duloxetine. The drug was capable of enhancing the threshold for the first myoclonic and tonic-clonic seizures induced by PTZ. Additionally, the EEG demonstrated that duloxetine at the dose of 20 mg/kg decreased significantly the amplitude of the waves while at the dose of 40 mg/kg it increased the amplitude when compared to all the treatments. Regarding the
evaluation of duloxetine’s influence on oxidative stress, all the animals treated solely with PTZ presented a significant increase on lipid peroxidation and a decrease on SOD and CAT activity. Concerning nitrites’ level, there was no difference between the treatments. The dose of 20 mg/kg of duloxetine showed a significant protection against the alterations in oxidative stress induced by PTZ. The anticonvulsant action of duloxetine (20 mg/kg) collaborates with the theory which has been presented in the last few years where it is proposed that the modulation of the serotonergic and noradrenergic neurotransmission may exert an anticonvulsant activity. Moreover, the efficiency of duloxetine in preventing the aggravation of oxidative stress involved in the seizures induced by PTZ corroborates with studies that demonstrate that anticonvulsant substances can influence seizures through its antioxidant activity. Given these points, we conclude that duloxetine is a promising adjuvant for the treatment of patients with the comorbidity epilepsy and depression.
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