Flumazenil antagonizes the effect of diazepam on negative contrast in one-way avoidance learning

The main aim of the present work was to study whether the effect of diazepam upon successive negative contrast in one-way avoidance learning-induced by shifting rats from a large reward (30s spent in the safe compartment) to a small reward (1s)-is mediated by the action of this drug on the benzodiazepine (BZ) receptor. Therefore, we studied the influence of flumazenil (FL), a BZ antagonist, on the effect of diazepam (DZ) on negative contrast. The i.p. administration of 5 and 12mg/kg, but not of 2mg/kg of FL, reliably antagonized the abolition by DZ (1mg/kg) on successive negative contrast. Moreover, FL (12mg/kg) did not affect either the avoidance response or the contrast effect. These results suggest that the GABA system is involved in the successive negative contrast effect in one-way avoidance learning, and that this experimental procedure may be useful in studies of anti-anxiety agents.