Pertussis toxin decreases absence seizures and GABA(B) receptor binding inthalamus of a genetically prone rat (GAERS)

Postsynaptic GABA(B) receptor-mediated events have previously been shown to be reduced by prior treatment with pertussis toxin in rat brain. In the pr esent study genetic absence epilepsy rats from Strasbourg (GAERS) were give n single bilateral injections of pertussis toxin (PTx 0.4 mu g), denatured- PTx or vehicle saline into the relay nuclei of the thalamus under anaesthes ia. After recovery the spike and wave discharge duration (SWD) was monitore d for up to 6 days following which the brains were removed and GABA(B) or G ABA(A) receptor autoradiography performed on TO mu m transverse sections. B y 6 days the SWD of the rats treated with PTx was suppressed by 96% compare d with vehicle-injected rats with a significant (62%) reduction even after 1 day. Denatured toxin had no effect at any time. After 6 days GABA(B), but not GABA(A), receptor binding was significantly reduced by 70-80% in the v entrolateral and ventral posteriolateral thalamic nuclei. No changes in oth er brain regions were detected and denatured toxin failed to alter GABA(A) or GABA(B) receptor binding in any brain region. These data implicate G-pro tein mechanisms in the generation of SWD in GAERS and support the role of G ABA(B) receptors in their induction within the thalamus. (C) 1999 Elsevier; Science Ltd, All rights reserved.