Evaluation of the Test-Retest Model of Anxiety in Mice

Hascoet      Martine; Michel      Bourin

Abstract

A test-retest protocol of an animal model of anxiety induces an increase of anxious behaviour and a loss of benzodiazepine induced effect. This effect mainly observed in the elevated plus maze, an ethological model of anxiety in mice, but also in the four plate test, a model based on punishment, was called the one trial tolerance. In the first step, a review of some hypotheses based on behavioural, pharmacological and neurochemical approaches is proposed to explain this benzodiazepines tolerance phenomenon on a test-retest model of anxiety, namely the four-plate test. Aversive memory consists of a diminution of the number of accepted punished passages. “One trial tolerance” is the abolishment of the anxiolytic-like effect of a drug in experimented mice. Diazepam, a usual benzodiazepine affected by one trial tolerance, is used in parallel with DOI, a 5-HT2A agonist that keeps its anxiolytic-like effect during retest, in order to study this phenomenon. Local injection of DOI and diazepam revealed that hippocampus was activated by DOI. Diazepam was active when injected into lateral nuclei of amygdala in naive mice, and into periaqueductal gray matter in experiment mice.

These results suggest that aversive memory and one trial tolerance seem triggered via different mechanisms, supported by different structures.

Keywords: Test-retest, one trial tolerance, anxiety models, four-plate test, Benzodiazepines (BZD), diazepam, hippocampus, barbiturates, Amygdala, Periaqueductal gray, Intra peritoneally, Periaqueductal gray matter, GABAA, chlordiazepoxide.