Enhancement of place and object recognition memory in young adult and old rats by RS 67333, a partial agonist of 5-HT4 receptors. 2001

L Lamirault, and H Simon
Laboratoire de Neuropsychobiologie des Désadaptations, CNRS UMR 5541, Université Victor Segalen Bordeaux 2, BP 31, 146, rue Léo Saignat, 33076 Cedex, Bordeaux, France. laetitia.lamirault@lnpb.u-bordeaux2.fr

There is recent evidence that activation of central 5-hydroxytryptamine (5-HT)4 receptors enhances cognitive processes such as learning and memory. In the present study, we assessed the effects of a selective 5-HT4 receptors agonist, RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone], in a two-trial recognition task designed to test place or object recognition memory.RS 67333 was injected in young adult (0.0001, 0.01, 1 mg/kg, i.p.) and old (0.0001, 0.01, 1, 10 mg/kg, i.p.) rats before the acquisition phase, immediately after it, or before the retrieval phase, to determine the stage of information processing affected by the compound. When injected before the acquisition phase, RS 67333 (1 mg/kg) enhanced place and object recognition in young adult rats. In old rats, RS 67333 (10 mg/kg) improved place recognition when injected before the acquisition phase, and object recognition when injected before the acquisition or in the consolidation phase of information processing. The beneficial effects of RS 67333 were abolished by prior treatment with a selective 5-HT4 receptors antagonist, GR 125487 [(1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate); 10 mg/kg, i.p.]. These results support the view that selective 5-HT4 receptors agonists may be of value in the treatment of cognitive disorders related to normal aging or neurodegenerative conditions such as Alzheimer's disease.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008297 Male Males
D008568 Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D010880 Piperidines A family of hexahydropyridines.
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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