Tolerance liability of diazepam is dependent on the dose used for protracted treatment

Background: behavioral effects of benzodiazepines following repeated exposure vary according to the intrinsic efficacy of the benzodiazepine studied,treatment schedule and the behavioral parameters evaluated. methods: we applied the behavioral paradigms of spontaneous locomotor activity,elevated plus maze and grip strength to investigate the sedative,anxiolytic and myorelaxant effect of acute challenge with 2 mg/kg diazepam administered after 14 days of protracted treatment with 0.5,2 or 10 mg/kg of diazepam. in addition,we studied the effects of everyday handling and intraperitoneal (ip) administration on animal behavior. results: tolerance to the sedative effect of 2 mg/kg diazepam ensued after 14 days of protracted treatment with 2 and 10 mg/kg of diazepam. in contrast,treatment with the lowest dose (0.5 mg/kg) of diazepam resulted in potentiation of the sedative effect of acute challenge with 2 mg/kg diazepam thus confounding the detection of the anxiolytic effect of diazepam. asensitization-like response to the anxiolytic action of 2 mg/kg diazepam was seen after protracted treatment with the intermediate dose (2 mg/kg); however,anxiolytic effect was absent after protracted administration of the highest dose. partial tolerance to the muscle relaxant effect of 2 mg/kg diazepam ensued after protracted treatment with diazepam regardless of the dose. daily handling or ip administration did not alter the behavioral response to acute challenge with 2 mg/kg diazepam in all the three behavioral paradigms studied. conclusion: the presented results showed that behavioral effects of acute challenge with diazepam were differently affected by the dose administered during protracted treatment. copyright © 2012 by institute of pharmacology polish academy of sciences.