title: Chronic activation of 5-HT4 receptors or blockade of 5-HT6 receptors improve memory performances.
abstract: 5-HT4 and 5-HT6 serotonergic receptors are located in brain structures involved in memory processes. Neurochemical and behavioural studies have demonstrated that acute activation of 5-HT4 receptors (5-HT4R) or blockade of 5-HT6 receptors (5-HT6R) improves memory. To evaluate the potential of these two receptors as targets in the treatment of memory disorders encountered in several situations (ageing, Alzheimer's disease, schizophrenia, etc.), it is necessary to assess whether their beneficial effects occur after chronic administration, and if such treatment induces adverse effects. The goal of this study was to assess the effects of chronic 5-HT4R or 5-HT6R modulation on recognition memory, and to observe the possible manifestation of side effects (modification of weight gain, locomotor activity or exploratory behaviour, etc.). Mice were treated for 14 days with a 5-HT4R partial agonist (RS-67333) or a 5-HT6R antagonist (SB-271046) at increasing doses. Memory performances, locomotor activity, and exploration were assessed. Both chronic 5-HT4R activation and 5-HT6R blockade extended memory traces in an object recognition test, and were not associated with any adverse effects in the parameters assessed. Chronic modulation of one or both of these receptors thus seems promising as a potential strategy for the treatment memory deficits.
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France. Electronic address: anne.quiedeville@orange.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Quiedeville
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Boulouard
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Hamidouche
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Da Silva Costa-Aze
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Nee
authors.affiliation: UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, EA 4258 CERMN, FR CNRS 3038 INC3 M, SF-4206 ICORE, Boulevard Becquerel, F-14032 Caen, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.affiliation: UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, EA 4258 CERMN, FR CNRS 3038 INC3 M, SF-4206 ICORE, Boulevard Becquerel, F-14032 Caen, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
authors.affiliation: UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, EA 4258 CERMN, FR CNRS 3038 INC3 M, SF-4206 ICORE, Boulevard Becquerel, F-14032 Caen, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fabis
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Freret
authors.affiliation: Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, F-14032 Caen, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Bouet
mesh_terms: D000704:Analysis of Variance; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000814:Aniline Compounds; D010880:Piperidines; D011985:Receptors, Serotonin; D058828:Serotonin 5-HT4 Receptor Agonists; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D044422:Receptors, Serotonin, 5-HT4; C107826:RS 67333; C117443:SB 271046
keywords: 5-HT4 and 5-HT6 receptors; Chronic administration; Mice; Recognition memory; Serotonin