Research article summary (published 30 Mar 2008):

The selective 5-HT6 receptor antagonists SB-271046 and SB-399885 potentiate NCAM PSA immunolabeling of dentate granule cells, but not neurogenesis, in the hippocampal formation of mature Wistar rats.

Full Abstract

While there is now substantial evidence that 5-HT(6) antagonism leads to significantly improved cognitive ability, the mechanism(s) and/or pathway(s) involved are poorly understood. We have evaluated the consequence of chronic administration of the 5-HT(6) receptor antagonists SB-271046 and SB-399885 on neural cell adhesion molecule polysialylation state (NCAM PSA), a neuroplastic mechanism necessary for memory consolidation. Quantitative analysis of NCAM PSA immunopositive neurons in the dentate gyrus of drug-treated animals revealed a dose-dependent increase in polysialylated cell frequency following treatment with both SB-271046 and SB-399885. These effects could not be attributed to increased neurogenesis, as no difference in the rate of bromodeoxyuridine incorporation was apparent between the control and drug-treated groups. A substantial increase in the frequency of polysialylated cells in layer II of the entorhinal and perirhinal cortices was also observed, brain regions not previously associated with neurogenesis. Chronic treatment with SB-271046 or SB-399885 also significantly increased the activation of dentate polysialylation that is specific to learning. This effect does not occur with other cognition-enhancing drugs, such as tacrine, and this action potentially differentiates 5-HT(6) receptor antagonism as an unique neuroplastic mechanism for cognitive processes which may slow or reverse age/neurodegenerative related memory deficits.

Author information

Author/s: Foley, Andrew G (AG); Hirst, Warren D (WD); Gallagher, Helen C (HC); Barry, Claire (C); Hagan, Jim J (JJ); Upton, Neil (N); Walsh, Frank S (FS); Hunter, A Jackie (AJ); Regan, Ciaran M (CM);

Affiliation: School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuropharmacology (Neuropharmacology), published in England. (Language: eng)

Reference: 2008-Jun; vol 54 (issue 8) : pp 1166-74

Dates: Created 2008/05/27; Completed 2008/08/25;

PMID: 18455201, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Antimetabolites - diagnostic use Bromodeoxyuridine - diagnostic use Cell Proliferation - drug effects Cytoplasmic Granules - drug effects; metabolism Dentate Gyrus - cytology; drug effects Dose-Response Relationship, Drug Entorhinal Cortex - cytology; drug effects Hippocampus - cytology; drug effects Immunohistochemistry Male

Maze Learning - drug effects Neural Cell Adhesion Molecules - pharmacology Neurons - drug effects; metabolism Piperazines - pharmacology Rats Rats, Wistar Receptors, Serotonin - drug effects Serotonin Antagonists - pharmacology Sialic Acids - pharmacology Sulfonamides - pharmacology Thiophenes - pharmacology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Antimetabolites (0) ; Neural Cell Adhesion Molecules (0) ; Piperazines (0) ; Receptors, Serotonin (0) ; SB 271046 (0) ; SB-399885 (0) ; Serotonin Antagonists (0) ; Sialic Acids (0) ; Sulfonamides (0) ; Thiophenes (0) ; polysialic acid (0) ; serotonin 6 receptor (0) ; Bromodeoxyuridine (59-14-3)

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