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Modulation of 5-HT7 receptor: effect on object recognition performances in mice

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Abstract

Objective

Recent data suggest that 5-HT7 receptors (5-HT7R) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HT7R in episodic-like memory, mice were administered 5-carboxamidotryptamine (5-CT, a 5-HT1A/1B/1D/7R agonist) and/or SB-269970 (a selective 5-HT7R antagonist) immediately after the acquisition session of the novel object recognition test.

Materials and methods

The object recognition test was performed in order to assess the effects of modulation of 5-HT7R during consolidation phase on episodic-like memory performances in mice. A protocol including 3 days of familiarisation to the apparatus has been realised in order to decrease the effect of novelty-induced arousal.

Results

With a 2-h delay, SB-269970 (3 and 10 mg/kg, administered subcutaneously) impaired the discrimination of the novel object. With a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with 5-CT (1 mg/kg) showed a significant discrimination. This promnesic effect with a long delay is effectively mediated by 5-HT7R activation since it was blocked by SB-269970 (10 mg/kg), but not by WAY-100135 (10 mg/kg) or by GR-127935 (10 mg/kg).

Conclusion

These data suggest that 5-HT7R tonically modulates cognitive processes involved in consolidation performances in object recognition. Therefore, 5-HT7R could be a promising target to treat memory dysfunctions (especially episodically related deficits) related to normal or pathological ageing.

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Acknowledgments

The authors would like to thank Emma McCallion and Dr. Eric T. MacKenzie for their English-editing advice.

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The authors declare that they have no conflict of interest related directly or indirectly to this work.

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Correspondence to Thomas Freret.

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All experiments comply with the current directives of the European Community and the French Agriculture and Forestry Ministry.

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Freret, T., Paizanis, E., Beaudet, G. et al. Modulation of 5-HT7 receptor: effect on object recognition performances in mice. Psychopharmacology 231, 393–400 (2014). https://doi.org/10.1007/s00213-013-3247-x

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