Effect of pre-training flumazenil administration on the acquisition of three different tasks in rats.

The central benzodiazepine receptor antagonist, flumazenil (5.0 mg/kg), given ip 30 min prior to training, enhanced retention test performance of step-down inhibitory avoidance in rats. A lower dose (2.0 mg/kg) given pre-training, or post-training was ineffective. The effect of flumazenil seems to result from an influence on acquisition, in spite of the fact that the drug did not alter training session performance. Pre-training flumazenil (5.0 mg/kg) also facilitated retention test performance of habituation to a buzzer, but not of habituation to an open field. The effect of flumazenil is not attributable to a general influence on inhibitory learning for the following reasons: 1) it enhanced acquisition of two different tasks in which behavioral inhibition plays entirely different roles; 2) it enhanced acquisition of one form of habituation but not of another; 3) data from the literature indicate that flumazenil also enhances acquisition of active avoidance. In the present experiments, the two tasks that were sensitive to the drug were more stressful or "anxiogenic" than the open field task. There is evidence from the literature that stress activates endogenous benzodiazepine-mediated mechanisms in the brain. The effect of flumazenil suggests that acquisition in stressful or anxiogenic circumstances may be normally down-regulated by such mechanisms.