Reduction of pentylenetetrazol-induced convulsions by the octadecaneuropeptide ODN.
Intracerebroventricular injection of the octadecaneuropeptide ODN in mouse, at doses of 12.5-1000 ng, reduced the percentage of convulsing animals and increased the latency of convulsions elicited by pentylenetetrazol (50 mg/kg, intraperitoneal [i.p.]). ODN also reduced the percentage of mortality induced by pentylenetetrazol (100 mg/kg, i.p.). The COOH-terminal octapeptide fragment of ODN was approximately equally effective but acted more rapidly than ODN to reverse the convulsant effect of pentylenetetrazol. ODN (100 ng, intracerebroventricular [i.c.v.]) increased the convulsion latency and reduced the percentage of animals that convulsed after the administration of the inverse agonist of benzodiazepine receptors DMCM (13 mg/kg, i.p.), whereas the benzodiazepine receptor antagonist flumazenil (1 mg/kg, subcutaneously) abrogated the protective effect of ODN (100 ng, i.c.v.) on pentylenetetrazol-induced convulsions. ODN (100 ng, i.c.v.) also reduced the percentage of DBA/2J mice displaying audiogenic convulsions. In contrast, ODN did not reduce the percentage of mice displaying tonic or clonic convulsions when electrical interauricular stimulations were applied. It is concluded that ODN, or more likely a proteolytic fragment derived from ODN, reduces pentylenetetrazol-induced convulsions through activation of central-type benzodiazepine receptors.
Garcia de Mateos-Verchere
J
J
Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23, Unité de Neuropsychopharmacologie, CNRS, UPRES-A 6036, Faculté de Médecine et Pharmacie, Université de Rouen, Saint-Etienne du Rouvray, France.
Leprince
J
J
Tonon
M C
MC
Vaudry
H
H
Costentin
J
J
D000161:Acoustic Stimulation; D000595:Amino Acid Sequence; D000818:Animals; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000633:toxicity; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D026261:Diazepam Binding Inhibitor; D004558:Electric Stimulation; D005442:Flumazenil / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D002243:Carbolines; D003292:Convulsants; D026261:Diazepam Binding Inhibitor; D009479:Neuropeptides; D010446:Peptide Fragments; D011963:Receptors, GABA-A; C067529:diazepam binding inhibitor (33-50); C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005442:Flumazenil; D010433:Pentylenetetrazole