Abstract
The effect of the serotonergic 5-HT4 receptor agonists BIMU 1 and BIMU 8 on in vivo acetylcholine (ACh) release in brain hemispheric regions of freely moving rats was investigated using the microdialysis technique. Both agonists, applied intracerebroventricularly, facilitated the release of ACh selectively in the frontal cortex and were ineffective in the striatum or dorsal hippocampus. The facilitatory effect of BIMU 1 in frontal cortex was prevented by the selective 5-HT4 receptor antagonists GR 125487 and GR 113808 which by themselves did not alter basal release. the results provide the first evidence that serotonin facilitates ACh release in frontal cortex through stimulation of 5-HT4 receptors which are not tonically activated. 5-HT4 receptor agonists might thus offer a novel means of boosting central cholinergic function to overcome the cholinergic deficit in memory disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism*
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Animals
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Benzimidazoles / antagonists & inhibitors
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Benzimidazoles / pharmacology
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Bridged Bicyclo Compounds / antagonists & inhibitors
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Bridged Bicyclo Compounds / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic*
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Female
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Frontal Lobe / drug effects
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Frontal Lobe / metabolism*
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Indoles / pharmacology
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Injections, Intraventricular
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Microdialysis
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Neostriatum / drug effects
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Neostriatum / metabolism
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Rats
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology*
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Sulfonamides / pharmacology
Substances
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Benzimidazoles
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Bridged Bicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Indoles
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Sulfonamides
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(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide
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(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide
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Acetylcholine
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GR 113808