title: SSP-002392, a new 5-HT4 receptor agonist, dose-dependently reverses scopolamine-induced learning and memory impairments in C57Bl/6 mice.
abstract: 5-HT4 receptors (5-HT4R) are suggested to affect learning and memory processes. Earlier studies have shown that animals treated with 5-HT4R agonists, often with limited selectivity, show improved learning and memory with retention memory often being assessed immediately after or within 24 h after the last training session. In this study, we characterized the effect of pre-training treatment with the selective 5-HT4R agonist SSP-002392 on memory acquisition and the associated long-term memory retrieval in animal models of impaired cognition. Pre-training treatment with SSP-002392 (0.3 mg/kg, 1.5 mg/kg and 7.5 mg/kg p.o.) dose-dependently inhibited the cognitive deficits induced by scopolamine (0.5 mg/kg s.c.) in two different behavioral tasks: passive avoidance and Morris water maze. In the Morris water maze, spatial learning was significantly improved after treatment with SSP-002392 translating in an accelerated and more efficient localization of the hidden platform compared to scopolamine-treated controls. Moreover, retention memory was assessed 24 h (passive avoidance) and 72 h (Morris water maze) after the last training session of cognitive-impaired animals and this was significantly improved in animals treated with SSP-002392 prior to the training sessions. Furthermore, the effects of SSP-002392 were comparable to galanthamine hydrobromide. We conclude that SSP-002392 has potential as a memory-enhancing compound.
authors.affiliation: Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium; Leuven Institute for Neuroscience & Disease (LIND), Leuven, Belgium.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Lo
authors.affiliation: Shire-Movetis NV, Veedijk 58, 1004 Turnhout, Belgium.
authors.forename: Joris H
authors.initials: JH
authors.lastname: De Maeyer
authors.affiliation: Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium; Leuven Institute for Neuroscience & Disease (LIND), Leuven, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Vermaercke
authors.affiliation: Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium; Leuven Institute for Neuroscience & Disease (LIND), Leuven, Belgium.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Callaerts-Vegh
authors.affiliation: Shire-Movetis NV, Veedijk 58, 1004 Turnhout, Belgium.
authors.forename: Jan A J
authors.initials: JA
authors.lastname: Schuurkes
authors.affiliation: Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium; Leuven Institute for Neuroscience & Disease (LIND), Leuven, Belgium. Electronic address: rudi.dhooge@ppw.kuleuven.be.
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005702:Galantamine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011897:Random Allocation; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012601:Scopolamine; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology
chemical_list: C000596157:4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid (3-hydroxy-1-(3-methoxypropyl)piperidin-4ylmethyl)amide; D001572:Benzofurans; D018697:Nootropic Agents; D010880:Piperidines; D058828:Serotonin 5-HT4 Receptor Agonists; D005702:Galantamine; D044422:Receptors, Serotonin, 5-HT4; D012601:Scopolamine
keywords: 5-HT(4); Cognition; Morris water maze; Passive avoidance; SSP-002392; Search strategies