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. H-3-Ro 15-1788 binding analysis provided evidence for a strong decrease in B-max in the resistant line. (C) 1998 Elsevier Science B.V.