Chronic exposure to Ro 15-1788: differential effect on flunitrazepam binding to cortex and hippocampus.
The time course of changes in specific [3H]flunitrazepam binding following 2 weeks of treatment with the benzodiazepine antagonist Ro 15-1788 (2.7 and 4 mg/kg per day in drinking water) was studied in the rat neocortical and hippocampal synaptosomal membranes. Such a treatment produced regional increases in the density of benzodiazepine sites, which remained for up to 24 and 48 h after drug withdrawal in the hippocampus and cortex, respectively; the dissociation constant (Kd) was unchanged. In addition, a significant reduction in GABA enhanced [3H]flunitrazepam binding to cortical, but not to hippocampal, membranes from Ro 15-1788-treated animals was found 72 h after drug withdrawal. These data show that there is a regional difference in responses of the GABA/benzodiazepine receptor complex following chronic in vivo exposure to Ro 15-1788 and that, beside the increases in the maximal binding (Bmax) of [3H]flunitrazepam the coupling between the GABA and the benzodiazepine recognition sites was also affected.
Urbancic
M
M
Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Marczynski
T J
TJ
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005442:Flumazenil / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam