Pentylenetetrazol-induced seizure is not mediated by benzodiazepine receptors in vivo.
The selective benzodiazepine antagonist RO 15-1788, labelled with carbon 11 [11C] RO 15-1788, as a specific marker, together with positron emission tomography, allows the in vivo study of benzodiazepine receptors in primates. In addition, when coupled with recordings of electroencephalographic activity, this method offers the feasibility of studying the correlation between occupancy of benzodiazepine receptors and the convulsant action of drugs acting at the benzodiazepine-GABA receptor complex in vivo. The present study showed that convulsant doses of pentylenetetrazol (PTZ) could affect the binding of [11C] RO 15-1788 in vivo in two ways, depending on the doses tested: at concentrations of 20 and 30 mg/kg, pentylenetetrazol increased the binding of [11C] RO 15-1788 whereas larger concentrations displaced the binding of [11C] RO 15-1788. The direct correlation between the occupancy of respective benzodiazepine receptors, afforded by increasing convulsant doses of pentylenetetrazol, revealed that competitive interaction with benzodiazepine receptors was not necessary for pentylenetetrazol to induce the appearance of seizures in vivo.
Hantraye
P
P
Service Hospitalier Frédéric Joliot, C.E.A., Département de Biologie, Orsay, France.
Brouillet
E
E
Guibert
B
B
Chavoix
C
C
Fukuda
H
H
Prenant
C
C
Crouzel
M
M
Naquet
R
R
Maziere
M
M
D000818:Animals; D004569:Electroencephalography; D005442:Flumazenil / Q000493:pharmacokinetics; D008297:Male; D010215:Papio; D010433:Pentylenetetrazole / Q000633:toxicity*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D011963:Receptors, GABA-A; D005442:Flumazenil; D010433:Pentylenetetrazole