Relationship of agonist efficacy to changes in GABA sensitivity and anticonvulsant tolerance following chronic benzodiazepine ligand exposure

Abstract

Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16-6028 and the antagonist, Ro 15-1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16-6028 and no changes were observed following chronic Ro 15-1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.