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: 4.6). 02/2008; 18(1):41-7. DOI: 10.1016/j.euroneuro.2007.04.006
Source: PubMed

ABSTRACT 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: Tolerance to the anxiolytic-like effect of drugs may develop because of a memory derived from prior experience in certain apparatuses such as the elevated plus-maze (EPM). Activity in basolateral amygdala was shown to be required for consolidating this knowledge. The dorsal hippocampus (DH) is also implicated in long-term memory consolidation, a process relying on new protein synthesis. It is unknown, however, whether the DH protein synthesis disruption would prevent the phenomenon rendering animals unresponsive to benzodiazepines in the EPM retest. To address this, we bilaterally infused the protein synthesis inhibitor anisomycin (ANI) into the rat DH 0, 3 or 6 h after, or 15 min before, the EPM test. DH infusion of ANI (80 μg) around the time of EPM testing preserved the anxiolysis of the midazolam (MDZ; 0.5 mg/kg, i.p.) in rats retested in the EPM 24 h later, suggesting that information consolidated by DH protein synthesis impacts on the subsequent animal's responsiveness to this drug. To examine whether impaired memory acquisition could also contribute to the prevention of MDZ tolerance seen in EPM-experienced animals infused with ANI before testing, the EPM retest was performed 3 h after testing to coincide with the temporal window in which short-term memory remains, for the reason that this process does not require protein synthesis for its formation. The pretest DH anisomycin infusion's ability to prevent the MDZ tolerance on retesting was now missing. This result confirms a specific action of the ANI on memory consolidation. We also found that rats express further avoidance to open-arms in the EPM retest. However, neither pretest nor posttest DH ANI infusion interfered with this pattern of results exhibited by EPM-experienced rats.
    Neuroscience 02/2011; 179:179-87. · 3.12 Impact Factor
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    ABSTRACT: Serotonin (5-HT) has been implicated in the regulation of the stress response. Two experiments were conducted to investigate the possibility that the 5-HT(2A), 2C agonist DOI would reduce behavioral responsiveness to stress, and that selective blockade of one or both of these receptor subtypes would reverse this effect. Stressors employed were mild tail pinch and an illuminated open field. In Experiment 1 DOI (0.1, 0.5, 1.0 mg/kg, s.c.) was found to decrease stress-evoked oral behavior directed at food and to increase rearing behavior in a dose-dependent fashion. Neither of these effects was reversed by spiperone (5-HT(2A) antagonist) or SDZ SER-082 (5-HT(2C) antagonist). DOI also increased the frequency of head shaking. This effect was reversed by SDZ SER-082. In Experiment 2 DOI was injected singly or in combination with ketanserin (5-HT(2A). 2C antagonist). DOI decreased tail pinch-evoked oral behavior directed at food, the amount of food eaten, and increased vocalization. In the open field DOI decreased rearing, increased the number of head shakes, and increased the incidence of flat body posture. While ketanserin alone (0.5, 2.5, 5.0 mg/kg) had no effect on any behavioral measure, coadministration of ketanserin (5.0 mg/kg) with DOI (0.5 and 1.0 mg/kg) significantly blocked the effects of DOI on oral behavior directed at food, eating, rearing, head shaking, and flat body posture. It is concluded that the observed effects of DOI on behaviors evoked by stress were mediated by activation of both 5-HT(2A) and 5-HT(2C) receptors.
    Pharmacology Biochemistry and Behavior 06/2008; 90(4):632-9. · 2.82 Impact Factor

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