Abstract
Generalized absence epilepsy is a neurological childhood disorder, which is characterized by behavioral arrest with string and by 3Hz spike and wave discharges (SWDs) in electroencephalography (EEG). γ-Butyrolactone (GBL) is the most used drug for animal model of absence seizure. We previously showed a dissociation of absence seizure and CRE-binding activity induced by GBL in the developing rat brain. The GBL is metabolized to γ-hydroxybutyric acid (GHB) and GHB further affects both on GABAB and GHB receptors. Thus, GABAB and GHB receptors are thought to be involved in generation of absence seizure. However the molecular mechanism of absence epilepsy mediated via GABAB and GHB receptors is not so clear until today. In the present study, we compared effect of GABAB and GHB on the EEG, behavior and CRE-binding activity in the adult mouse brain by using receptor-specific agonists and antagonists. A low dose (40 mg/kg) of baclofen, a specific GABAB receptor agonist induced a typical absence seizure of arrest in behavior, SWDs in EEG and CRE-binding activity in the mouse brain. The change in behavior, EEG and transcriptional activity continued for a long time (>2 hr). In contrast, a high dose (200mg/kg) of GHB induced only CRE-binding activity but not typical change of EEG. The action of GHB did not continue so long (<45 min). These results also show a dissociation of absence seizure and CRE-binding activity in the adult mouse brain. [Jpn J Physiol 54 Suppl:S214 (2004)]
