Abstract
The effects of BIMU-8, a 5-HT4 receptor agonist, were studied on GABA release in guinea pig hippocampal slices. BIMU-8 did not modify GABA outflow at rest but did display a complex action in electrically stimulated slices: at low concentrations it increased, and at higher concentrations inhibited, GABA release. These responses were competitively counteracted by GR 125487, a selective 5-HT4 receptor antagonist. The dual effects of BIMU-8 are consistent with its indirect cholinergic action since the M1 and M3 antagonist, 4-DAMP, prevented BIMU-8-elicited GABA facilitation, whereas the M2 antagonist AFDX-116 cancelled GABA inhibition. These results provide evidence that serotonin exerts a complex modulation on the GABAergic system, via 5-HT4 receptors, and suggest that the amine releases acetylcholine which, in turn, bidirectionally modulates GABA release.
MeSH terms
-
Acetylcholine / metabolism
-
Animals
-
Benzimidazoles / pharmacology
-
Bridged Bicyclo Compounds, Heterocyclic / pharmacology
-
Dose-Response Relationship, Drug
-
Electric Stimulation
-
Female
-
GABA Antagonists / pharmacology
-
Guinea Pigs
-
Hippocampus / drug effects
-
Hippocampus / metabolism*
-
Male
-
Muscarinic Antagonists / pharmacology
-
Neurons / drug effects
-
Neurons / metabolism*
-
Organ Culture Techniques
-
Receptors, Serotonin / drug effects
-
Receptors, Serotonin / metabolism*
-
Receptors, Serotonin, 5-HT4
-
Serotonin / metabolism*
-
Serotonin / pharmacology
-
Serotonin Antagonists / pharmacology
-
Serotonin Receptor Agonists / pharmacology
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology*
-
Tetrodotoxin / pharmacology
-
gamma-Aminobutyric Acid / metabolism*
Substances
-
Benzimidazoles
-
Bridged Bicyclo Compounds, Heterocyclic
-
GABA Antagonists
-
Muscarinic Antagonists
-
Receptors, Serotonin
-
Serotonin Antagonists
-
Serotonin Receptor Agonists
-
(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide
-
Receptors, Serotonin, 5-HT4
-
Serotonin
-
Tetrodotoxin
-
gamma-Aminobutyric Acid
-
Acetylcholine