Antonio Leo1, Carmen De Caro1, Valentina Nesci1, Ernesto Palma1, Martina Tallarico2, Michelangelo Iannone3, Andrew Constanti4, Giovambattista De Sarro1, Emilio Russo1, Rita Citraro5. 1. University of Catanzaro, School of Medicine, Science of Health Department, Catanzaro, Italy. 2. University of Catanzaro, School of Medicine, Science of Health Department, Catanzaro, Italy; CNR, Institute of Neurological Sciences, Pharmacology Section, Roccelletta di Borgia, Catanzaro, Italy. 3. CNR, Institute of Neurological Sciences, Pharmacology Section, Roccelletta di Borgia, Catanzaro, Italy. 4. Department of Pharmacology, UCL School of Pharmacy, London, UK. 5. University of Catanzaro, School of Medicine, Science of Health Department, Catanzaro, Italy. Electronic address: citraro@unicz.it.
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.
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.
Authors: Martina Tallarico; Antonio Leo; Lorenza Guarnieri; Maria Caterina Zito; Carmen De Caro; Ferdinando Nicoletti; Emilio Russo; Andrew Constanti; Giovambattista De Sarro; Rita Citraro Journal: Mol Neurobiol Date: 2022-02-15 Impact factor: 5.590
Authors: Benjamin F Gruenbaum; Mani Ratnesh S Sandhu; Raphael A O Bertasi; Tais G O Bertasi; Antonia Schonwald; Anirudh Kurup; Shaun E Gruenbaum; Isaac G Freedman; Melissa C Funaro; Hal Blumenfeld; Gerard Sanacora Journal: Epilepsia Date: 2021-03-10 Impact factor: 6.740