RO-15-4513 POTENTIATES, INSTEAD OF ANTAGONIZES, ETHANOL-INDUCED SLEEPIN MICE EXPOSED TO SMALL PLATFORM STRESS

The effects of ethanol and the benzodiazepine receptor ligand azido-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5a] [1,4] benzodiazepine-3-carb oxplate (Ro 15-4513), were examined in NMRI mice exposed to small plat form stress. This model contains several factors of stress, like rapid eye movement (REM) sleep deprivation, isolation, immobilization, fall ing into water and soaking. In control mice, ethanol exerted an anxiol ytic effect in the plus-maze, but did not further enhance the anxiolyt ic-like effects induced by small platform stress. Ro 15-4513 antagoniz ed ethanol-induced sleep in control animals, but enhanced the hypnotic and lethal actions of ethanol in small platform stressed mice. Small platform stress did not alter the characteristics (K-D and B-max) of [ H-3]Ro 15-4513 binding to cerebellar membranes. Muscimol-stimulated Cl -36(-) uptake into brain microsacs was significantly reduced in cortex from small platform stressed animals. Ethanol had no effect on Cl-36( -) uptake into brain microsacs from cortex or cerebellum It is propose d that small platform stress alters the activity of the gamma-aminobut yric acid (GABA)(A) receptor-chloride ionophore complex, causing chang es in the interaction between ethanol and Ro 15-4513.