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Factors triggering abolishment of benzodiazepines effects in the four-plate test-retest in mice.

Petit-Demoulière B, Hascoët M, Bourin M

EA 3256 "Neurobiologie de l'anxiété et de la dépression", Faculté de Médecine, BP 53508, 1 Rue Gaston Veil, F44035 Nantes Cedex 01 France.

Abolishment of anxiolytic-like effects of diazepam occurs during re-exposure to some animal tests of anxiety. We investigated the loss of anxiolytic-like effects of diazepam during Trial 2 on previously undrugged mice, namely one-trial tolerance (OTT). Swiss mice were subjected to 1) Four-Plate Test (FPT) without punishments in Trial 1 or 2) FPT without punishments in both Trials or 3) FPT with spatial modifications in Trial 1 or 4) Elevated Plus Maze (EPM), then 24 h later to FPT, with saline, diazepam (1 mg/kg) or DOI (1 mg/kg). Removing punishments in Trial 1 does not counteract the effect reduction of diazepam in Trial 2, but spatial modifications of the aversive environment. Previous exposure to EPM does not trigger a loss of efficacy of diazepam in FPT. Electric punishments do not trigger OTT to benzodiazepines; whilst knowledge of the environment seems to be responsible for this phenomenon. FPT may be useful to study OTT because punishments potentate OTT in this model of anxiety.

Published 10 December 2007 in Eur Neuropsychopharmacol, 18(1): 41-7.
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