Antagonism of 5-HT1Areceptors uncovers an excitatory effect of SSRIs on 5-HT neuronal activity, an action probably mediated by 5-HT7receptors

Autor: Joost H.A. Folgering, Anne W. Schmidt, Jeffrey Sprouse, Anatoliy V. Gladkevich, Thomas I. F. H. Cremers, Johan A. den Boer, Marieke C. G. van der Hart, Ben H.C. Westerink, Fokko J. Bosker
Přispěvatelé: Biomonitoring and Sensoring, Medicinal Chemistry and Bioanalysis (MCB)
Rok vydání: 2009
Předmět:
Male
DORSAL RAPHE NUCLEUS
Pyrrolidines
raphe nucleus
Pyridines
hippocampus
Microdialysis
WAY 100
Action Potentials
SB 258741
Biochemistry
Piperazines
Tosyl Compounds
chemistry.chemical_compound
Serotonin Agents
Piperidines
Electrochemistry
Drug Interactions
citalopram
Receptor
Neurotransmitter
EXTRACELLULAR 5-HYDROXYTRYPTAMINE
Chromatography
High Pressure Liquid
Neurons
Brain
Receptor
Serotonin
5-HT1A
Antidepressant
ELECTROPHYSIOLOGICAL RESPONSES
PHARMACOLOGICAL CHARACTERIZATION
Selective Serotonin Reuptake Inhibitors
Agonist
Serotonin
medicine.medical_specialty
Tetrahydronaphthalenes
medicine.drug_class
Serotonin reuptake inhibitor
Serotonin 5-HT1 Receptor Antagonists
Biology
RAT-BRAIN
RELEASE INVIVO
Cellular and Molecular Neuroscience
AS19
Internal medicine
medicine
Animals
Rats
Wistar
Wakefulness
5-HT receptor
Analysis of Variance
PIG
ADENYLYL-CYCLASE
IN-VITRO
Rats
Endocrinology
nervous system
chemistry
Receptors
Serotonin
SEROTONIN TRANSPORTER
Pyrazoles
Raphe nuclei
Zdroj: Journal of Neurochemistry, 108(5), 1126-1135. Blackwell Publishing Ltd
ISSN: 1471-4159
0022-3042
DOI: 10.1111/j.1471-4159.2008.05850.x
Popis: Both microdialysis and electrophysiology were used to investigate whether another serotonin (5-HT) receptor subtype next to the 5-HT(1A) autoreceptor is involved in the acute effects of a selective serotonin reuptake inhibitor on 5-HT neuronal activity. On the basis of a previous study, we decided to investigate the involvement of the 5-HT(7) receptors. Experiments were performed with the specific 5-HT(7) antagonist SB 258741 and the putative 5-HT(7) agonist AS19. In this study WAY 100.635 was used to block 5-HT(1A) receptors. Systemic administration of SB 258741 significantly reduced the effect of combined selective serotonin reuptake inhibitor and WAY 100.635 administration on extracellular 5-HT in the ventral hippocampus as well as 5-HT neuronal firing in the dorsal raphe nucleus. In the microdialysis study, co-administration of AS19 and WAY 100.635 showed a biphasic effect on extracellular 5-HT in ventral hippocampus, hinting at opposed 5-HT(7) receptor mediated effects. In the electrophysiological experiments, systemic administration of AS19 alone displayed a bell-shaped dose-effect curve: moderately increasing 5-HT neuronal firing at lower doses while decreasing it at higher doses. SB 258741 was capable of blocking the effect of AS19 at a low dose. This is consistent with the pharmacological profile of AS19, displaying high affinity for 5-HT(7) receptors and moderate affinity for 5-HT(1A) receptors. The data are in support of an excitatory effect of selective serotonin reuptake inhibitors on 5-HT neuronal activity mediated by 5-HT(7) receptors. It can be speculated, that the restoration of 5-HT neuronal firing upon chronic antidepressant treatment, which is generally attributed to desensitization of 5-HT(1A) receptors alone, in fact results from a shift in balance between 5-HT(1A) and 5-HT(7) receptor function.
Databáze: OpenAIRE
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