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Increased particulate phosphodiesterase 4 in the prefrontal cortex supports 5-HT4 receptor-induced improvement of object recognition memory in the rat

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Abstract

Rationale

Serotonin receptors (5-HT4Rs) are critical to both short-term and long-term memory processes. These receptors mainly trigger the cyclic adenosine monophosphate (cAMP)/protein kinase A signaling pathway, which is regulated by cAMP phosphodiesterases (PDEs).

Objectives

We investigated the mechanisms underlying the effect of the selective activation of 5-HT4R on information acquisition in an object recognition memory task and the putative regulation of PDE.

Materials and methods

The effect of RS 67333 (1 mg/kg, intraperitoneally [i.p.], injected 30 min before the sample phase) was examined at different delay intervals in an object recognition task in Sprague–Dawley rats. After the testing trial, PDE activity of brain regions implicated in this task was assayed.

Results

RS 67333-treated rats spent more time exploring the novel object after a 15-min (P < 0.001) or 4-h delay (P < 0.01) but not after a 24-h delay, whereas control animals showed no preference for the novel object for delays greater than 15 min. We characterized the specific patterns and kinetic properties of PDE in the prefrontal and perirhinal cortices as well as in the hippocampus. We demonstrated that particulate PDE activities increase in both the prefrontal cortex and hippocampus following 5-HT4R stimulation. In the prefrontal cortex, PDE4 activities support the RS 67333-induced modification of PDE activities, whereas in the hippocampus, all cAMP-PDE activities varied. In contrast, particulate PDE variation in the hippocampus was not found to support improvement of recognition memory after a 4-h delay.

Conclusions

We provide evidence that the increase in particulate PDE4 activity in the prefrontal cortex supports the 5-HT4R-induced increase in information acquisition.

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Acknowledgments

The authors thank Dr. S. Carreau (Laboratoire Œstrogènes et Reproduction, EA 2608, INRA USC 2006, University of Caen) and Dr. P. Barbey (LAMARE) for giving us access to the ultracentrifuge and the radioactivity laboratory, respectively. The authors also want to thank Dr. Daryl S Henderson (Squirrel Scribe) for final language revision. This work was supported by grants from the University of Caen.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie-Physiologie, Centre d’Etudes et de Recherche sur le Médicament de Normandie, Université de Caen Basse–Normandie, Caen, France

    Guénaëlle Levallet, Maïté Hotte, Michel Boulouard & François Dauphin

  2. Groupe Mémoire et Plasticité Comportementale, UFR des Sciences Pharmaceutiques, Université de Caen Basse–Normandie, Caen, France

    Maïté Hotte, Michel Boulouard & François Dauphin

  3. Laboratoire d’Histologie, Bureau 03-114, CHU de Caen, Avenue de la côte de Nacre, 14032, Caen, France

    Guénaëlle Levallet

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  1. Guénaëlle Levallet
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  4. François Dauphin
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Correspondence to Guénaëlle Levallet.

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Levallet, G., Hotte, M., Boulouard, M. et al. Increased particulate phosphodiesterase 4 in the prefrontal cortex supports 5-HT4 receptor-induced improvement of object recognition memory in the rat. Psychopharmacology 202, 125–139 (2009). https://doi.org/10.1007/s00213-008-1283-8

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