Opposite effects of GABAB receptor antagonists on absences and convulsive seizures.

Abstract In Wistar rats with spontaneous non-convulsive absence epilepsy, absence seizures were dose dependently suppressed by intraperitoneal administration of the GABA B receptor antagonists CGP 36742, 50–400 mg/kg, and CGP 56999, 0.25–0.75 mg/kg, and by bilateral microinjections of the same compounds into the lateral nuclei of the thalamus. In rats susceptible to audiogenic seizures, intraperitoneal administration of both GABA B receptor antagonists, at doses which suppressed absence seizures, facilitated the elicitation of sound-induced tonic seizures. In non-epileptic control rats, intraperitoneal injections of higher doses of CGP 36742 (800–2400 mg/kg) and CGP 56999 (3–6 mg/kg) induced delayed clonic convulsions, which were suppressed by pretreatment with baclofen. c-Fos protein was expressed after GABA B receptor antagonist-induced seizures in the cortex, hippocampus, amygdala, perirhinal and piriform cortex. Intra-cortical and hippocampal microinfusion of both GABA B receptor antagonists produced focal seizures. In conclusion, GABA B receptor antagonists suppress non-convulsive absence seizures by blocking thalamic GABA B receptors, while they induce convulsions in cortical and limbic structures.