Paper
Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats
Published Jan 1, 1981 · S. File
Psychopharmacology
31
Citations
1
Influential Citations
Abstract
Acute administration of lorazepam (0.25 and 0.5 mg/kg) and triazolam (0.075–0.25 mg/kg) significantly reduced the locomotor activity of rats placed in a holeboard for 10 min. Acute injections of lorazepam (0.25 and 0.5 mg/kg) and triazolam (0.05–0.25 mg/kg) also significantly reduced exploration, measured by the number of head-dips and the time spent head-dipping. After 3 days of pretreatment, tolerance developed to the sedative effects of these drugs: lorazepam (0.25 mg/kg) and triazolam (0.05 and 1 mg/kg) were without significant effect, and lorazepam (0.5 mg/kg) had only the effect of half that dose given acutely. Some of this behavioural tolerance could be attributed to changes in drug metabolism, and the development of tolerance did not require continuous presence of drug in brain and plasma.
Non-RCT
Animal Study
Rigorous JournalTolerance to the sedative effects of lorazepam and triazolam rapidly develops in rats after 3 days of pretreatment, with some of this tolerance attributed to changes in drug metabolism.
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