Factors triggering abolishment of benzodiazepines effects in the Four-Plate Test--retest in mice.

EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, BP 53508, 1 Rue Gaston Veil, F44035 Nantes Cedex 01 France.
European Neuropsychopharmacology (Impact Factor: 4.37). 02/2008; 18(1):41-7. DOI: 10.1016/j.euroneuro.2007.04.006
Source: PubMed


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.

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    ABSTRACT: Anxiolytic-like effect of diazepam is abolished by a previous exposure to four-plate test (FPT). Variations of temporal parameters: interval between trials and duration of Trial 1, with or without electric punishments allow characterizing factors which are responsible for this loss phenomenon. Complete spatial representation of FPT seems to be responsible of this one-trial tolerance, and needs at least a 30s exposure to the apparatus to be completed, with or without punishments.
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    ABSTRACT: Four-plate test-retest (FPT-R) is a useful tool to study aversive memory and abolishment of benzodiazepine effects in experienced mice to four-plate test (FPT), namely one-trial tolerance. In the present study, we have used local injections paradigm, in order to localize structures implied in anxiolytic-like effects of two drugs in naïve and experienced mice: a benzodiazepine, diazepam that is only active in naïve mice; and a 5-HT(2A/2C) agonist, DOI that exert its anxiolytic-like effect both in naïve and experienced mice. Periacqueductal grey substance, three sub-regions of hippocampus (CA1, CA2 and CA3) and two nuclei of amygdala (BLA and LA) have been studied. Local injections did not cause any modifications of ambulatory activity. DOI injections elicit anxiolytic-like effects only when injected into CA2, in naïve and experienced mice. Diazepam had an anxiolytic-like effect in naïve mice, only when injected into lateral nucleus of amygdala; and in experienced mice when injected into PAG. These results help us to better understand the way of action of these two compounds and the structures functionally involved in their effects and in one-trial tolerance (OTT).
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