SIMILAR EFFECTS OF ETHANOL AND FLUMAZENIL ON ACQUISITION OF A SHUTTLE-BOX AVOIDANCE-RESPONSE DURING WITHDRAWAL FROM CHRONIC ETHANOL TREATMENT

1 Acquisition of a two-way shuttle-box avoidance response is facilitat ed by ethanol. This facilitated acquisition of an avoidance response t o ethanol was attenuated during withdrawal from chronic-ethanol diet i ntake (i.e. tolerance developed by ethanol). The deficit in the avoida nce task after chronic ethanol treatment could be overcome by increasi ng the dose of ethanol. 2 Flumazenil, a benzodiazepine antagonist, als o facilitated acquisition of the avoidance response in control rats. T his response to flumazenil was significantly reduced during withdrawal from chronic-ethanol treatment. This reduced avoidance responding dur ing withdrawal also could be overcome by increasing the dose of flumaz enil. 3 The benzodiazepine-inverse agonist, RO 15-4513, produced a def icit in avoidance responding that was antagonized by both ethanol and flumazenil in a dose-related manner. 4 To determine whether flumazenil has the properties of a benzodiazepine agonist, it was established th at, unlike the benzodiazepine chlordiazepoxide, flumazenil did not enh ance the ethanol-induced deficit in the aerial righting reflex. Additi onally, flumazenil blocked the action of chlordiazepoxide in this proc edure, consistent with the benzodiazepine antagonist action of flumaze nil. 5 Data collected are consistent with the hypothesis that an endog enous substance with the properties of a benzodiazepine-inverse agonis t antagonizes the anticonflict actions of acutely administered ethanol during withdrawal from chronic-ethanol exposure.