Enhanced selective attention after low-dose administration of the benzodiazepine antagonist flumazenil

Although recognized for their sedative properties, benzodiazepines are also known to impair sustained and selective attention. Flumazenil at low doses may act to antagonize benzodiazepine-induced effects. This study examined whether low doses of flumazenil would improve event-related brain potential (ERP) indicators of selective attention and induce feelings of activation and anxiety in healthy men. Data from 11 men (24-30 years) who received intravenous flumazenil (0.2 mg, plus 0.3 mg 30 minutes later) and placebo were analyzed according to a double-blind crossover design. ERPs were recorded while subjects performed an auditory selective attention task. Mismatch negativity (MMN), processing negativity (PN), and the P3 component were extracted from the ERP as markers of preattentive mismatch processing, selective attention, and stimulus processing within working memory, respectively. Counting accuracy and performance on a letter cancellation test were used as behavioral indicators of attention. Mood was assessed by an adjective checklist and the State-Trait Anxiety Inventory. Flumazenil significantly increased PN over frontocortical areas, indicating improved selective attention (p < 0.05). Increases in the P3 amplitude and MMN after drug treatment remained nonsignificant. Subjects felt more activated and extraverted after flumazenil treatment than after placebo (p < 0.05). Anxiety was not increased. The findings of this study confirm the concept that flumazenil administered at a low dose in humans exerts effects opposite to those of benzodiazepines.