Reversal of diazepam‐induced impairment in successive discrimination performance by flumazenil

Abstract

AbstractThe effects of diazepam (DZ) alone and in combination with flumazenil (Ro 15‐1788) on the performance of a previously learned successive discrimination task were studied in male Sprague‐Dawley rats. DZ 4 mg/kg impaired discrimination performance in five successive sessions, although animals showed some tolerance to the drug's action. The impairment in discrimination performance was due to an increase in responding during no go periods of the task (errors of commission). The benzodiazepine (BDZ) receptor antagonist flumazenil (5 and 10 mg/kg) partially reversed the impairment in discrimination performance and reduced the number of incorrect responses in a generally dose‐dependent manner when coadministered with DZ. These findings suggest that the impairment in discrimination performance by DZ is mediated by central BDZ receptor sites. When administered alone, flumazenil 10 mg/kg (but not 5 mg/kg) produced a mild impairment in discrimination performance which, in contrast to DZ's effects, was due to both small increases in no go period responses (errors of commission) and small decreases in go period responses (errors of omission). These findings suggest that flumazenil is not a neutral antagonist but has some intrinsic action of its own. © 1992 Wiley‐Liss, Inc.