Tolerance to the behavioral actions of benzodiazepines

The evidence for tolerance to the behavioral effects in animals of benzodiazepines is reviewed. Tolerance develops rapidly (within 3-5 days) to the sedative effects and from 5 days of treatment to the anticonvulsant effects. In general, tolerance has not been found to anxiolytic effects after 7-15 days of treatment, although in the social interaction test it was found after 25 days. Tolerance has not been found to the locomotor stimulant effects up to 20 days of treatment. Dispositional tolerance does not occur following treatment with low doses and nor is there clear evidence of changes in benzodiazepine binding. Such changes could not account for the very different rates of tolerance to the different behavioral effects, but these could be explained if learned adaptation were to underlie tolerance or to influence the rate at which it develops. Whether the mechanism of learned adaptation is one of instrumental conditioning, classical conditioning or habituation will depend on the formal aspects of the test. It is therefore suggested that the different rates of tolerance are a function of the detailed arrangement of the experimental situation and not of the particular behavior measured or of the clinical effect the test is meant to reflect.