title: Chronic administration of diazepam downregulates adenosine receptors in the rat brain.
abstract: Following chronic administration (10 or 20 days) of diazepam (5 mg/kg/day, subcutaneous pellets) or RO 15-1788 (5 mg/kg/day, intraperitoneally), adenosine and benzodiazepine receptors in different rat brain areas were assessed by radioligand binding studies using [3H]R-PIA for A1 receptors, [3H]NECA and [3H]R-PIA for A2 receptors and [3H]FNZ for benzodiazepine receptors. Chronic administration of diazepam for 10, but not for 20 days, decreased A2 receptors in the striatum by 46% (p less than 0.05) and A1 receptors in the hippocampus by 13% (p less than 0.05). Administration of diazepam for 10 days and 20 days failed to alter [3H]FNZ binding in all brain areas studied. However, 20 days of diazepam administration decreased the magnitude of GABA enhancement of [3H]FNZ binding in the cortex by 25% (p less than 0.05). In contrast, chronic administration of RO 15-1788 failed to alter [3H]R-PIA, [3H]NECA and [3H]FNZ binding in all brain areas. These results suggest that adenosine receptors may play a role in the CNS actions of benzodiazepines.
authors.affiliation: Department of Pharmacology, University of Illinois, College of Medicine, Chicago 60612.
authors.forename: M
authors.initials: M
authors.lastname: Hawkins
authors.forename: M
authors.initials: M
authors.lastname: Pravica
authors.forename: M
authors.initials: M
authors.lastname: Radulovacki
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; D005442:Flumazenil; D005445:Flunitrazepam; D003975:Diazepam