Long Term Antiepileptic Drugs Treatment, Absence Epilepsy and Depression: a Correlation Study
S. De Fazio1, E. Russo1, R. Citraro1, F. Scicchitano1, P. De Fazio1, C. Segura Garcia1, P. Gareri1 and G. De Sarro1.
1 Dept. of Experimental and Clinical Medicine, School of Medicine, University of Catanzaro, Italy
Absence Epilepsy causes generalized seizure mainly affecting children, its pathognomic features are represented by EEG 3Hz Spike-Wave Discharges (SWDs) and an abrupt loss of consciousness (Russo et al., 2004). Recently some authors assessed a putative relationship between epilepsy and depressive behavior, while some others supposed that the two clinical entities might represent different neuropathological profile of the same underlying neurological disorder (Jobe, 2003). The WAG/Rij rats, a validated animal model of absence epilepsy, have been proposed as a suitable tool to prove the effectiveness of antidepressant protective factors (Sarkisova et al., 2008). Very recently, using the above mentioned model, Antiepileptic Drugs (AEDs) were tested in a long term study in order to assess their protective role in epilptogenic processes rather than their pure anticonvulsant properties (Russo et al., in press). The aim of this study is to establish the role of a long term treatment with AEDs on both seizure disappearance and depressive like behavior onset, using Porsolt Forced swimming test (FST). Long term (4 months) AEDs-treated WAG/Rij rats were tested, after four weeks since drugs discontinuation, in the forced-swim test (FST), according to the original two-day procedure described by Porsolt et al. (1977). Animals were initially divided into one untreated control group (5 rats), and into 4 equally numbered treated group with Carbamazepine, Zonisamide, Levetiracetam, and Ethosuximide. On the first day (pre-test session), between 09,00 and 12,00 hours a.m., each rat was individually plunged in a plexiglas cylinder (height 33 cm x diameter 20 cm), containing 25 cm of tap water at a temperature of 25° C and placed inside a sound attenuated room were a 100-W lamp was the only source of illumination. The animals were left to swim in the clean water for 15 min before being removed, were gently dried with a towel and returned to their home cage. Twenty-four hours later (test session day), the rats were re-exposed to the tank for 5 min and the session was recorded using a webcam connected to a notebook. The animal’s behavior during the first 5 min period of FST was later scored as activity (presence of movements) and immobility (absence of movements). A mouse was judged to be immobile when it remained floating in the water, making only those movements necessary to keep its head above the water (Porsolt et al., 1977). EEG recordings from each group, as previously described by Russo et al (2004), were obtained after two weeks from FST performing. During FST a double counting analysis was performed and then compared with a double blinded counting obtained through videos examination. Control group WAG/Rij rats were judged in an immobility state for about 64 seconds, while both carbamazepine and zonisamide treated animals had a 55 seconds immobility, with no or mild effect on SWDs reduction, respectively. On the contrary Ethosuximide treated animals showed a reduction in immobility time of 36.7 seconds, with a significative reduction of EEG recorded SWDs. Levetiracetam was able to induce an immobility time augmentation (64 seconds), showing a protective effect on seizure reduction. While both levetiracetam and ethosuximide long term treatment is able to reduce seizure occurrence, caution should be focused on the depressive behavior onset, which seems to be unrelated to seizure control, and on which Ethosuximide exerts protective effect.
Jobe (2003). Epilepsy Behav. 4, S14-24.
Russo et al. Epilepsia. in press.
Porsolt et al. (1977). Nature. 266, 730-2.
Russo et al. (2004). Neuropharmacology 46: 865–878.
Sarkisova et al. (2008). Neurosci Behav Physiol. 38, 119-28.