Withdrawal, tolerance and sensitization after a single dose of lorazepam

Forty-eight hours after a single dose of lorazepam (0.25 mg/kg), there was tolerance to the lorazepam-induced reduction of locomotor activity in the holeboard; but no tolerance to the reductions in exploratory head-dipping or rearing. Mice tested undrugged at this time showed significant hyperactivity and increased rearing, indicating withdrawal responses, but no change in head-dipping. In the elevated plus-maze, no tolerance could be detected to the effects of lorazepam (0.25 mg/kg) when the mice were tested 48 hr after an initial dose; in fact, there was a trend towards enhanced effects in this group. When mice were tested undrugged 24, 48 or 72 hr after a single dose of lorazepam there was an increase in the % time spent on the open arms, compared with controls, that reached significance for the 24 hr group. This indicates a sensitization to the anxiolytic effects of lorazepam, as assessed in the plus-maze. These results demonstrate long-lasting effects of even a single dose of lorazepam.