Characterization of absence seizure-dependent cyclic AMP responsive element- and activator protein 1 DNA-binding activities in lethargic (lh/lh) mice

The characterized nuclear cyclic AMP responsive element (CRE)- and activato r protein 1 (AP-1) DNA-binding activities in various brain regions of letha rgic (lh/lh) mice, a genetic model of absence seizures. Gel-shift assays sh owed that nuclear CRE- and AP-1 DNA-binding activities in the thalamus and cerebral cortex, but not in other regions such as the hippocampus and cereb ellum of lethargic mice were significantly higher than those of non-epilept ic control mice. Furthermore, CRE- and AP-I DNA-binding activities in letha rgic mice, but not control mice, were inhibited by the specific GABA(B) rec eptor antagonist CGP 46831, at a dose which suppressed seizure behavior and spike and wave discharges. These results suggest that enhanced nuclear CRE - and AP-I DNA-binding activities in the thalamocortical region are related to generation and/or propagation of absence seizures in lethargic mice. (C ) 1999 Elsevier Science Ireland Ltd. All rights reserved.