Effects of the imidazobenzodiazepine RO15-4513 on the stimulant and depressant actions of ethanol on spontaneous locomotor activity.

The purpose of this study was to investigate the effects of the imidazobenzodiazepine RO15-4513, a partial inverse agonist at benzodiazepine (BDZ) receptors, on the stimulant and depressant actions of ethanol in mice. For comparative purposes, another BDZ inverse agonist, FG-7142, was examined as well. Neither RO15-4513 nor FG-7142 influenced the low-dose excitatory effects of ethanol on spontaneous locomotor activity. However, both RO15-4513 and FG-7142 significantly antagonized the depressant effects of ethanol, and this antagonism was completely reversed by pretreatment with the BDZ receptor antagonist, RO15-1788. These data suggest that RO15-4513 is capable of antagonizing only some of the behavioral effects of ethanol, and in particular, those responses to ethanol that are mediated by modulation of the GABA/BDZ-chloride channel receptor complex.