Benzodiazepine tranquilizers, phenazepam and flunitrazepam, administered to random-bred albino male rats in superlow doses (109-10 -is mol/kg), are shown to exert an anxiolytic effect in the conflicttest, in contrast to the case with the usual doses, the above effect is not accompanied by marked myorelaxant or sedative effects.

Phenazepam administered in superlow doses exerts an anxiolytic effect in albino male rats under conditions of plus-maze and conflict test and induces typical inhibition of 0-activity in the EEG. Contrary to the effect of usual doses, other frequency intervals remain practically unchanged. Phenazepam in superlow doses acts as an anxioselective tranquilizer. Key Words: tranquilizers; phenazepam; superlow doses; EEG; anxiolytic activitySince benzodiazepines usually have various side effects, new approaches to pharmacotherapy of neurosis-like and borderline-neurotic states are directed toward anxioselectivity of the treatment. It has been previously demonstrated that phenazepam in low doses (up to 10 -1~ mol/kg) exerts a pronounced anxiolytic effect under conditions of a conflict situation without inducing adverse effects [3].Our goal was to evaluate electrophysiological effects of low doses of phenazepam and their relationship with rat behavior in different models of anxiety. MATERIALS AND METHODSExperiments were carried out on random-bred albino male rats with initial body weight of 200-220 g.The EEG was recorded under conditions of free behavior [6] using a Neurograph 18-channel electroencephalograph (O.T.E. Biomedica) with amplifiers set at a standard mode: 0. After initial habituation, the background EEG was recorded for 5 min. Phenazepam (10 -1~ mol/kg) was administered intragastrally through a tube; EEG was recorded and analyzed every 15 rain during the first hour and then every hour. Control animals received placebo according to the same scheme. The effects of phenazepam administered in superlow and usual doses were compared.Anxiolytic activity of phenazepam was assessed in the standard conflict test [5,13] and in elevated plus-maze test [9].The conflict situation test is based on a conflict between drinking motivation and painful electrical stimulation in water-deprived animals. A considerably increased number of punished drinkings in the experimental group in comparison with the control served as a measure of the effect.The

Phenazepam in ultralow doses produced an anxiolytic effect on male outbred albino rats in the conflict situation and elevated plus-maze models and inhibited theta-activity in EEG, which is typical of tranquilizers. As differentiated from standard doses, phenazepam in this concentration did not affect other frequency bands. Our results suggest that phenazepam in ultralow doses acts as the anxioselective tranquilizer.