Genetic selection of mouse lines differing in sensitivity to a benzodiazepine receptor inverse agonist.
Mice were selectively bred according to their sensitivity or their resistance to the convulsive effects of a 4-mg/kg dose of methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine (BZ) receptor inverse agonist. The selection proved to be easy, with a clear separation of the two lines, convulsing with short latencies or resistant, already at the first generation of selection. Selection of a third line of animals convulsing with long latencies did not succeed. 3H-Ro 15-1788 binding analysis provided evidence for a strong decrease in Bmax in the resistant line.
Chapouthier
G
G
Génétique, Neurogénétique, Comportement (UPR CNRS 9074), 3B rue de la Férollerie, 45071 Orléans Cedex 02, France.
Launay
J M
JM
Venault
P
P
Breton
C
C
Roubertoux
P L
PL
Crusio
W E
WE
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D012641:Selection, Genetic; D013045:Species Specificity
D002243:Carbolines; D003292:Convulsants; D018682:GABA Agents; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester