Does RO 15-4513 reverse the anxiolytic effects of ethanol by its intrinsic properties?

Abstract

In order to better understand the antagonistic effects of the partial inverse agonist of benzodiazepine receptors, RO 15-4513, against the disinhibitory action of ethanol, we examined the effects of RO 15-4513 at a dose (2.0 mg/kg) that did not alter locomotor activity, given alone or in combination with ethanol, on the behavior of mice confronted with the light/dark choice procedure and the staircase test. At this dose, RO 15-4513 given alone was found to have slight anxiogenic properties and when given in combination with ethanol, to completely reverse the disinhibitory effects of ethanol. Since we previously observed postictal depression after higher doses of RO 15-4513 given alone and antagonistic effects of these same doses on the action of ethanol, it can be suggested that the antagonistic effects of RO 15-4513 against ethanol are due to its anxiogenic or depressive properties depending on doses. However, this hypothesis can only be regarded as being in early stages of development at the present time since these results do not parallel with those of several other studies and the question whether the antagonistic action of RO 15-4513 against ethanol is additive or interactive remains open.