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Animal Model Studies of Benzodiazepine-Induced Amnesia

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Benzodiazepine Receptor Ligands, Memory and Information Processing

Part of the book series: Psychopharmacology Series ((PSYCHOPHARM,volume 6))

Abstract

The development of a mouse passive avoidance test as a model for amnesia produced by benzodiazepines is described. The model appropriately classifies the amnesic potential of a wide range of psychoactive drugs as validated by clinical findings. Control experiments indicate that the effect is best described as anterograde amnesia resulting from a failure of consolidation. γ-Aminobutyric acid (GABA) antagonists had almost no effect on benzodiazepine-induced amnesia, whereas the benzodiazepine-receptor antagonist Ro 15–1788 completely and specifically reversed it. This clinically confirmed finding suggests that benzodiazepine-induced amnesia is mediated through the benzodiazepine-receptor. However, in vivo inhibition of benzodiazepine binding does not correlate well with amnesia in the mouse, and some benzodiazepine-receptor agonists with potent CNS effects in other in vitro models do not produce amnesia. Additional work is needed to clarify what aspects of benzodiazepine receptor occupancy mediate amnesia.

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Author notes

  1. E. R. Gamzu

    Present address: Clinical Research Department, Warner Lambert/Parke-Davis, 2800 Plymouth Rd., Ann Arbor, MI, 48105, USA

Authors and Affiliations

  1. Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ, 07110, USA

    E. R. Gamzu

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  1. E. R. Gamzu
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Editors and Affiliations

  1. Human Psychopharmacology Research Unit, University of Leeds, LS2 9JT, Leeds, UK

    Ian Hindmarch (Head) (Head)

  2. Research Laboratories Department Pharmacopsychology, Schering AG, P. O. Box 65 03 11, 1000, Berlin 65, Federal Republic of Germany

    Helmut Ott

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© 1988 Springer-Verlag Berlin Heidelberg

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Gamzu, E.R. (1988). Animal Model Studies of Benzodiazepine-Induced Amnesia. In: Hindmarch, I., Ott, H. (eds) Benzodiazepine Receptor Ligands, Memory and Information Processing. Psychopharmacology Series, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73288-1_16

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  • DOI: https://doi.org/10.1007/978-3-642-73288-1_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73290-4

  • Online ISBN: 978-3-642-73288-1

  • eBook Packages: Springer Book Archive

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