A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures.
The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5-60 mg/kg dose range, beta-CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to beta-CCM. Both the Ta gene and the TaTfm/Gnc genetic background were involved in the high resistance to beta-CCM. In addition, concentrations of neurosteroids and benzodiazepine binding, both modulating GABAA receptor efficacy, have been measured in order to elucidate the biological mechanisms of drug resistance.
Clément
Y
Y
U.R.A C.N.R.S. 1294, U.F.R Biomédicale, Université Paris V, France.
Launay
J M
JM
Bondoux
D
D
Venault
P
P
Martin
B
B
Young
J
J
Robel
P
P
Chapouthier
G
G
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002243:Carbolines; D003292:Convulsants; D004351:Drug Resistance / Q000235:genetics; D005069:Evaluation Studies as Topic; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010433:Pentylenetetrazole; D011280:Pregnanolone / Q000032:analysis*; D011284:Pregnenolone / Q000032:analysis*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000032:analysis*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics*
D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; C018370:pregnenolone sulfate; D011284:Pregnenolone; D011280:Pregnanolone; C036150:beta-carboline-3-carboxylic acid methyl ester; D010433:Pentylenetetrazole