Pertussis toxin decreases absence seizures and GABA(B) receptor binding in thalamus 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 present study genetic absence epilepsy rats from Strasbourg (GAERS) were given single bilateral injections of pertussis toxin (PTx 0.4 microg), denatured-PTx or vehicle saline into the relay nuclei of the thalamus under anaesthesia. After recovery the spike and wave discharge duration (SWD) was monitored for up to 6 days following which the brains were removed and GABA(B) or GABA(A) receptor autoradiography performed on 10 microm transverse sections. By 6 days the SWD of the rats treated with PTx was suppressed by 96% compared 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 ventrolateral and ventral posteriolateral thalamic nuclei. No changes in other 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-protein mechanisms in the generation of SWD in GAERS and support the role of GABA(B) receptors in their induction within the thalamus.
Bowery
N G
NG
Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, UK. n.g.bowery@bham.ac.uk
Parry
K
K
Boehrer
A
A
Mathivet
P
P
Marescaux
C
C
Bernasconi
R
R
D000818:Animals; D004569:Electroencephalography / Q000187:drug effects*; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018080:Receptors, GABA-B; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins