VIGABATRIN CHANGES THE PROPERTIES OF SPIKE AND WAVE DISCHARGES IN A RAT MODEL FOR ABSENCE EPILEPSY
Abstract number :
2.127
Submission category :
Year :
2003
Submission ID :
2514
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Brigitte M. Bouwman, Piotr Suffczynski, Clementina M. van Rijn NICI/dept. Biological Psychology, University of Nijmegen, Nijmegen, Netherlands; dept. of Medical Physics, Dutch Epilepsy Clinics Foundation, Heemstede, Netherlands
Absence epilepsy, which is mostly seen in children, is a mild form of epilepsy characterized by generalized Spike and Wave Discharges (SWDs) accompanied by short lapses in consciousness. There are several antiepileptic drugs (AEDs) available for treatment. However, these available drugs are not relieving all patients of their seizures, thus new AEDs are necessary. Knowledge about the mechanisms and neurotransmitters involved in seizure initiation and termination allows for a target-oriented approach in the AED development. The neurotransmitter gamma-aminobutyric acid (GABA) is generally believed to be involved in the underlying mechanisms of (absence) epilepsy. Therefore, further research on the influence of GABAergic drugs on specific parameters of these SWDs might lead to better understanding of the mechanisms involved in these epileptic phenomena.
In the present study, the effects of vigabatrin (VGB) on SWDs in the EEG of WAG/Rij rats were studied. VGB is an irreversible GABA transaminase inhibitor which increases, long lasting, GABA concentrations. The WAG/Rij rat, an inbred strain of rats, is recognized as an animal model of human absence epilepsy. The SWDs were studied in WAG/Rij rats after inter-peritoneal injection of 15-500 mg/kg of VGB, six hours after injection.
The incidence of the SWDs was dose dependently increased after VGB, from 25 /h after saline to 129 /h after 500 mg/kg of VGB. The mean duration of the SWDs was not affected (6.8 s). The peak-frequency of the SWDs was dose dependently decreased after VGB, from 8.9 Hz after saline to 7.0 Hz after the highest dose of VGB. Furthermore, despite the unaffected mean SWD duration, the distribution of the SWD durations and the durations of the SWD free intervals (inter SWD duration) differed between the saline (Gaussian distributed) and the 500 mg/kg VGB group (exponentially distributed).
These results show that VGB alters not only the incidence and the peak frequency of the SWDs, but also their temporal properties. The distribution of the SWD durations and the inter SWD durations, indicates that termination and initiation of SWDs occur randomly in time after 500 mg/kg of VGB, whereas they are governed by deterministic mechanisms in the saline group. These results further underline the important role of GABAergic neurotransmission in the underlying mechanisms of absence epilepsy.
[Supported by: The Dutch National Epilepsy Fund supported this study (NEF 20-08).]