Anxiolytic-like effect of 5-HT2 ligands and benzodiazepines co-administration: Comparison of two animal models of anxiety (the four-plate test and the elevated plus maze)

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Animal models of anxiety remain a useful tool for evaluating the anxiolytic-like effect of new treatments. Even though many tests are similarly based on exploration tasks, using more than one animal model is all the more recommended since there are qualitative differences between such tests. Furthermore, although many tests are excellent tool for detecting benzodiazepines/GABA compounds, inconsistent results have been reported for 5-HT ligands. Here, two animal models have been chosen, the elevated plus maze (EPM) based on the natural aversion of rodents for open spaces and the four-plates test (FPT) a models involving the animal's conditioned response to stressful events. In a recent study, we have demonstrated that the 5-HT2A/2C agonist DOI and the 5-HT2B agonist BW 723C86 were shown to produce an anxiolytic-like effect in both tests.

This study aimed to evaluate a putative interaction between benzodiazepine and 5-HT2 ligands in the FPT and the EPM. Indeed, close distribution of GABAA and 5-HT2 receptors was found in brain structures leading to functional interrelation.

In the FPT, sub-active doses of alprazolam and diazepam were strongly potentiated by DOI. BW 723C86, also potentiated the anxiolytic-like effect of the two benzodiazepines with a weaker effect. In the same way, DOI and benzodiazepines administration induced an increase in the anxiolytic-like parameters in the EPM with a strongest effect observed with alprazolam. Regardless of anxiety models used in this study, 5-HT2A ligands exerted facilitatory influence upon GABAergic system. Therefore, the FPT and the EPM might implicate the same kind of anxiety.

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