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.
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S E
SE
UMDS Division of Pharmacology, University of London, Guy's Hospital, UK.
Wilks
L J
LJ
Mabbutt
P S
PS
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D004361:Drug Tolerance; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013997:Time Factors
D008140:Lorazepam