Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release.

Full Abstract

The involvement of the cholinergic system in learning and memory together with the cognitive enhancing properties of 5-HT6 receptor antagonists led us to study the relationship between 5-HT6 receptors and cholinergic neurotransmission. A selective cholinergic lesion, induced by injection of the immunotoxin 192-IgG-Saporin into the nucleus basalis magnocellularis, failed to alter the density of 5-HT6 receptor mRNA or protein expression in the deafferentated frontal cortex, suggesting that 5-HT6 receptors are not located on cholinergic neurons. The 5-HT6 receptor antagonist SB-357134 (0.001-1 microM) induced a concentration-dependant K+-evoked [3H]acetylcholine (ACh) release in vitro in rat cortical and striatal slices, which was blocked by tetrodotoxin. SB-357134, up to 1 microM, stimulated glutamate release in cortical and striatal slices. In the cortex, riluzole (1 microM) blocked the SB-357134-induced K+-stimulated [3H]ACh release, and simultaneous administration of MK-801 (1 microM) and SB-357134 (0.05 microM) elicited an increase in K+-evoked ACh release. In the striatum, SB-357134, 1 microM, decreased dopamine release, and the increase in K+-evoked [3H]ACh release induced by 5-HT6 receptor blockade was reversed by the D1 receptor antagonist, SCH23390 (1 microM). In both the frontal cortex and striatum, bicuculline, 1 microM, showed no effect on SB-357134-evoked [3H]ACh. These results are discussed in terms of neurochemical mechanisms involved in 5-HT6 receptor functions.

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Author information

Author/s: Marcos, Beatriz (B); Gil-Bea, Francisco J (FJ); Hirst, Warren D (WD); García-Alloza, Mónica (M); Ramírez, María J (MJ);

Affiliation: Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.

Journal and publication information

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

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2006-Sep; vol 24 (issue 5) : pp 1299-306

Dates: Created 2006/09/21; Completed 2006/11/14; Revised 2007/11/15;

PMID: 16987217, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholine - metabolism
Analysis of Variance
Animals
Antibodies, Monoclonal - administration & dosage
Brain - cytology; drug effects; metabolism
Cholinergic Agents - administration & dosage
Dizocilpine Maleate - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Antagonists - pharmacology
Immunotoxins - administration & dosage
In Situ Hybridization - methods
Male

Male
N-Glycosyl Hydrolases
Neurons - drug effects; metabolism
Neurotransmitter Agents - classification; metabolism
Piperazines - pharmacology
Potassium - pharmacology
Radioligand Assay - methods
Rats
Rats, Wistar
Receptors, Serotonin - physiology
Ribosome Inactivating Proteins, Type 1
Sulfonamides - pharmacology
Tritium - metabolism

Associated Chemicals: 192 IgG-saporin (0) ; Antibodies, Monoclonal (0) ; Cholinergic Agents (0) ; Excitatory Amino Acid Antagonists (0) ; Immunotoxins (0) ; N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (0) ; Neurotransmitter Agents (0) ; Piperazines (0) ; Receptors, Serotonin (0) ; Ribosome Inactivating Proteins, Type 1 (0) ; Sulfonamides (0) ; serotonin 6 receptor (0) ; Tritium (10028-17-8) ; Acetylcholine (51-84-3) ; Potassium (7440-09-7) ; Dizocilpine Maleate (77086-22-7) ; N-Glycosyl Hydrolases (EC 3.2.2.-)

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