, Volume 82, Issue 3, pp 161–163 | Cite as

Long-lasting single-dose tolerance to neurologic deficits induced by diazepam

  • Stephan A. Henauer
  • Edward J. Gallaher
  • Leo E. Hollister
Original Investigations


Development of single-dose tolerance to diazepam-induced neurologic deficits was assessed in mice by means of a rotarod test. Diazepam suspended in corn oil was administered orally in doses 5–20 mg/kg. Tolerance was found following a second administration of diazepam 24 h after a first dose. It decayed gradually over 4–5 weeks. Hence tolerance persists considerably longer than measurable amounts of diazepam or its metabolites are likely to be present in mice.

Key words

Diazepam Single-dose tolerance Rotarod test Ataxia Neurologic deficits 


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  1. Barnett A, Fiore JW (1973) Acute tolerance to diazepam in cats. In: Garattini S (ed) The benzodiazepines. Raven Press, New York, pp 545–557Google Scholar
  2. Caccia S, Carli M, Garattini S, Poggesi E, Rech R, Samanin R (1980) Pharmacological activities of clobazam and diazepam in the rat: Relation to drug brain levels. Arch Int Pharmacodyn Ther 243:275–283Google Scholar
  3. Dunham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharmacol Assoc 46:208–209Google Scholar
  4. File SE (1981) Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats. Psychopharmacology 73:240–245Google Scholar
  5. Garattini S, Mussini E, Marcucci F, Guaitani A (1973) Metabolic studies on benzodiazepines in various animal species. In: Garattini S (ed) The benzodiazepines. Raven Press, New York, pp 75–97Google Scholar
  6. Giles HG, McLeod SM, Wright JR, Sellers EM (1978) Influence of age and previous use of diazepam dosage required for endoscopy. Can Med Assoc J 118:513–514Google Scholar
  7. Gluckman MI, Baxter BL (1971) Comparative effects of single and repeat dose administration of minor tranquilizers. Psychopharmacology Bull 7 (4):26–28Google Scholar
  8. Goldberg ME, Manian AA, Efron DH (1967) A comparative study of certain pharmacologic responses following acute and chronic administrations of chlordiazepoxide. Life Sci 6:481–491Google Scholar
  9. Mandelli M, Tognoni G, Garattini S (1978) Clinical pharmacokinetics of diazepam. Clin Pharmacokinetics 3:72–91Google Scholar
  10. Overstreet DH, Yamamura HI (1979) Minireview: Receptor alterations and drug tolerance. Life Sci 25:1865–1878Google Scholar
  11. Rosenberg HC, Chiu TH (1981) Tolerance during chronic benzodiazepine treatment associated with decreased receptor binding. Eur J Pharmacol 70:453–460Google Scholar
  12. Sansone M (1979) Effects of repeated administration of chlordiazepoxide on spontaneous locomotor activity in mice. Psychopharmacology 66:109–110Google Scholar
  13. Vorne MS, Puolakka JO, Idanpaan-Heikkila JE (1975) Diazepam, ethanol and drug metabolizing enzymes in rat liver. Arch Int Pharmacodyn Ther 216:280–287Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • Stephan A. Henauer
    • 1
  • Edward J. Gallaher
    • 1
  • Leo E. Hollister
    • 1
  1. 1.Veterans Administration Medical CenterPalo AltoUSA

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