Leo, A;
De Caro, C;
Nesci, V;
Palma, E;
Tallarico, M;
Iannone, M;
Constanti, A;
... Citraro, R; + view all
(2019)
Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary.
Pharmacological Reports
, 71
(5)
pp. 833-838.
10.1016/j.pharep.2019.04.017.
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Abstract
Background: WAG/Rij rats represent a validated genetic animal model of epileptogenesis, absence epilepsy and depressive-like comorbidity. Some treatments (e.g. ethosuximide), using specific protocols, prevent the development of spontaneous absence seizures. Accordingly, ethosuximide increases remission occurrence in children with childhood absence epilepsy in comparison to valproic acid. Considering that in this animal model, antiepileptogenic effects are, in some cases, not retained over time, we studied whether the antiepileptogenic effects of both ethosuximide and levetiracetam (which also possesses antiepileptogenic effects in this and other animal epilepsy models) would be retained 5 months after drug suspension. Methods: WAG/Rij rats of ~1 month of age were treated long-term with one of the two drugs at a dose of ~80 mg/kg/day for 17 consecutive weeks; 1 and 5 months after drug suspension, the development of absence seizures as well as depressive-like behaviour were assessed by EEG recordings and the forced swimming test (FST). Results: In agreement with a previous report, both drugs continued to show antiepileptogenic effects 1 month after their discontinuation. Furthermore, ethosuximide improved depressive-like behaviour, whereas in contrast, levetiracetam worsened this symptom. However, none of the drugs maintained their antiepileptogenic effects 5 months after suspension, and in addition, animal behaviour in the FST returned to control conditions. Conclusion: Overall, these results demonstrate that the antiepileptogenic effects of both ethosuximide and levetiracetam on absence seizure development and associated depressive-like behaviour in this model are only temporary.
| Type: | Article |
|---|---|
| Title: | Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.pharep.2019.04.017 |
| Publisher version: | https://doi.org/10.1016/j.pharep.2019.04.017 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Ethosuximide; Levetiracetam; Epileptogenesis; Absence epilepsy; Depressive behaviour. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072881 |
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