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Chronic diazepam treatment: Effect of dose on development of tolerance and incidence of withdrawal in an animal test of anxiety
Author(s) -
Sandra E.
Publication year - 1989
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.470040111
Subject(s) - diazepam , anxiety , medicine , anesthesia , anxiolytic , animal model , psychology , pharmacology , psychiatry
The effect of the treatment dose of diazepam was assessed on the rate of development of tolerance to diazepam's effects on rat behaviour in the elevated plus‐maze test of anxiety. Tolerance developed more rapidly when treatment was with the higher dose: after 14 days when rats were given 2·5 mg/kg/day, but not until 21 days when they were given 1 mg/kg/day. When rats were tested undrugged 36 h after the last of 14 daily doses of diazepam (2·5 mg/kg) they showed behavioural changes indicating increased anxiety. Rats tested at this time with a lower dose of diazepam (1 mg/kg) also showed changes indicating increased anxiety compared with the control scores. This indicates that a more gradual tapering of doses would be necessary to avoid withdrawal responses.