Effects of new antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.

Several studies with larvae and adult zebrafish have shown that old and new antiseizure drugs (ASDs) produce discrepant results in seizure tests, locomotor activity or anxiety models. In this study, the pentylenetetrazole seizure test (PTZ) was performed to assess the effectiveness of four new ASDs: lamotrigine (LTG), topiramate (TPM), felbamate (FBM), and levetiracetam (LEV) in the subsequent stages of seizures in adult fish. All ASDs were administered intraperitoneally (i.p.). The time of maximal anticonvulsant effect and the dose-response relationship of the drugs were assessed. The effects of studied ASDs on the locomotor activity and the anxiety-like behavior in the color preference test were also investigated. Furthermore, drug concentrations in zebrafish homogenates were determined. LTG, TPM, and LEV significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII), while FBM was effective only at SI. Locomotor activity decreased after TPM treatment. TPM and FBM exhibited a strong anxiolytic-like effect in the color preference test. LEV at the highest dose tested had a weak anxiolytic-like effect. The HPLC analysis showed average concentrations of the studied ASDs in the fish body during their maximum anticonvulsant activity. The present study shows that FBM cannot inhibit all subsequent PTZ seizure stages in the adult fish. Except for LTG, the studied drugs affected the anxiety-like behavior of treated animals. Furthermore, only TPM significantly changed locomotion parameters. Our findings support the need to accurately characterize the efficacy of new ASDs at different stages of the PTZ-induced seizures in adult zebrafish.

Comparison of immunological, histological and oxidative effects of felbamate and levetiracetam in traumatic brain injury.

OBJECTIVE: We aimed to compare immunological, histological and oxidative effects of antiepileptic agents; felbamate and levetiracetam on head trauma in rats. MATERIALS AND METHODS: In this study, 32 Sprague-Dawley genus male rats were used. A closed head trauma mechanism was constituted in order to perform head trauma in rats. Rats were divided into 4 groups, and each group had 8 rats. Following head trauma, Group 1 (Control); normal saline was administered, Group 2; levetiracetam 50 mg/kg was administered, Group 3; felbamate 100 mg/kg was administered, and Group 4; levetiracetam 50 mg/kg and felbamate 100 mg/kg were administered with a combination. Injections were administered intraperitoneally once a day for 20 days. The rats were decapitated at the end of the 20th day. Blood and tissue samples were collected and analyzed for biochemical, immunohistochemical and histological parameters. RESULTS: Serum cytokine levels in Group 2, 3 and 4 were lower when compared to the control group. In Group 4, in which combined therapy was performed, cytokine levels were found to be the lowest. In Groups 2 and 3, a significant decrease in vascular congestion, mononuclear cell infiltration, hemorrhage, and neural degeneration was noticed in the pia mater. In Group 2, a decrease in vascular congestion and Purkinje cell degeneration was obtained in the cerebellum. However, the best outcomes were determined in Group 4. CONCLUSIONS: We determined that levetiracetam and felbamate alone are useful with respect to immunological, oxidative and histological alterations. However, their utility is better when used in a combination.

Felbamate produces antidepressant-like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression.

Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant-like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant-like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS-stressed and CSDS-stressed mice. Collectively, felbamate has antidepressant-like actions in mice involving the hippocampal BDNF system.