Effects of chronic flunitrazepam treatment schedule on therapy-induced sedation and motor impairment in mice.

BACKGROUND The aim of the present study was to examine whether different treatment schedules could be associated with tolerance development to the ataxic and sedative effects of flunitrazepam in mice. METHODS Effects of repeated flunitrazepam administration were studied in the rotarod and the chimney test for motor coordination and in a photocell apparatus for locomotor activity in mice. Flunitrazepam doses varied in particular types of injections or in different experiment duration periods. RESULTS Repeated flunitrazepam administration (1 mg/kg, sc and 2 mg/kg, ip) for 8 consecutive days induced tolerance to the motor impairing effects of flunitrazepam in mice, both in the rotarod and the chimney test. In turn, no tolerance developed to sedative flunitrazepam effects, regarding either dose level, injection type or treatment duration. CONCLUSIONS Those findings confirmed the previous observations that tolerance to benzodiazepines was not simultaneous for each pharmacological property of the drugs. Interestingly enough, an acute dose of flunitrazepam (1 mg/kg, sc) in our study enhanced locomotor activity of mice.