Low-dose alprazolam augments motor activity in mice.

The triazolobenzodiazepine alprazolam appears to have a unique clinical spectrum, and recent studies indicate unusual binding properties at the benzodiazepine receptor when assessed in vivo at low doses (0.02-0.05 mg/kg). To assess the behavioral activity of alprazolam at low doses, we examined open-field activity after one hour in mice treated with alprazolam, triazolam, and clonazepam. Following triazolam and clonazepam administration, open-field activity decreased in a dose-dependent fashion. In contrast, low doses of alprazolam resulted in an increase in open-field activity, whereas higher doses decreased activity. For all three drugs, activity was linearly related to receptor binding. Pretreatment with a dose of the benzodiazepine antagonist Ro15-1788 sufficient to fully occupy receptors had no effect on open-field activity, but when administered concurrently with alprazolam (0.05 mg/kg) prevented the increase in activity seen with alprazolam alone. Increased open-field motor activity represents a behavioral correlate to the increases in receptor binding seen with low-doses of alprazolam. Changes in activity appear to be mediated at the benzodiazepine receptor, since an antagonist prevents increased activity. These data suggest that the unique clinical effects of alprazolam may be due in part to unusual interactions with the benzodiazepine receptor.