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


OBJECTIVE
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.


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.
Levallet
Guénaëlle
G
Laboratoire de Pharmacologie-Physiologie, Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Caen Basse-Normandie, Caen, France. levallet-g@chu-caen.fr
Hotte
Maïté
M
Boulouard
Michel
M
Dauphin
François
F
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D006234:Handling, Psychological; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects*; D020889:Rolipram / Q000494:pharmacology; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000814:Aniline Compounds; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C107826:RS 67333; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram