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Behavioural Effects in Mice of Subchronic Buspirone, Ondansetron and Tianeptine. II. The Elevated Plus-Maze

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Abstract

In follow-up to recent work on benzodiazepines (chlordiazepoxide) and selective monoamine reuptake inhibitors (maprotiline and fluvoxamine), the present study compares the effects of the 5-HT1A receptor partial agonist, buspirone (0.75–3.0 mg/kg), the 5-HT3 receptor antagonist, ondansetron (0.1–100 μg/kg), and the novel antidepressant, tianeptine (2.5–10.0 mg/kg), on the behaviour of mice in the elevated plus-maze test of anxiety. Compounds were administered daily for 21 days prior to testing, and an ethological scoring technique was used to generate comprehensive behavioural profiles. Results show that subchronic treatment with ondansetron failed to influence the behaviour of mice in the plus-maze, while the limited changes induced by buspirone could not be attributed to anxiety-related processes. In contrast, tianeptine produced unambiguous anxiogenic-like effects at the top dose tested (10.0 mg/kg), a profile that was not secondary to changes in general levels of locomotor activity or exploration. Data are discussed in relation to current pharmacotherapy of anxiety and depressive disorders, and the nature of anxiety induced by animal models.

Section snippets

Animals

Subjects were adult male CD1 mice (Charles River, U.K.), weighing 23–45g and housed in groups of 10 (cage size: 45 × 28 × 13 cm) for 3 weeks prior to the experiment. They were maintained under a reversed 12h LD cycle (lights off: 0700h) in a temperature (21 ± 1°C)- and humidity (50 + 5%)-controlled environment. Food and water were freely available. All mice were experimentally naive.

Drugs

Drugs used were buspirone hydrochloride (Sigma, U.K.), ondansetron hydrochloride (formerly GR38032F; Glaxo Group

Results

Table 1 summarizes the main ANOVA statistics, and reveals significant treatment effects on several of behavioural measures. For clarity, the results of follow-up analyses are presented under appropriate sub-headings.

Discussion

The current study involved daily handling and injection of subjects for 21 days. In view of the possible impact of such experience on behavioural baselines [64], the design incorporated both saline-injected and uninjected controls. Our results (Table 2) confirm earlier findings [67]in that the chronic handling/injection regimen employed had minimal effect upon behavioural baselines in male CD1 mice. It is also pertinent to note that the behavioural profile of intact male CD1 mice in the

Acknowledgements

This work was supported by MRC. We are grateful to Glaxo Group Research (UK) and Servier France for the kind gifts of ondansetron and tianeptine, respectively.

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