title: Effects of the 5-HT(4) receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels.
abstract: The 5-HT(4) receptor modulates activity of serotonergic neurons and is a new potential target for antidepressant treatment. This microdialysis study evaluated the effect of the 5-HT(4) receptor agonist, RS67333, on extracellular serotonin (5-hydroxytryptamine, 5-HT) and 5-HIAA levels in rat ventral hippocampus during chloral hydrate anaesthesia, and explored the ability of RS67333 to augment the effect of the selective serotonin reuptake inhibitor paroxetine. The effect of RS67333 was examined after acute and subchronic (3 days) administration. Acute RS67333 (1.5mg/kg i.v.) had no effect on extracellular 5-HT or 5-HIAA levels, while acute paroxetine (0.5mg/kg i.v.) increased 5-HT levels by 299+/-16% and decreased 5-HIAA levels by 25+/-4%. Administration of RS67333 80 min after paroxetine caused an additional transient increase in 5-HT levels (to 398+/-52% of baseline). Subchronic RS67333 administration (1.5mg/kg i.p.) increased basal 5-HT levels by 73+/-15% and decreased 5-HIAA levels by 27+/-13%. In conclusion, the 5-HT(4) receptor agonist RS67333 augmented the acute effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus, and after 3 days increased basal hippocampal 5-HT levels.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), University of Copenhagen and Rigshospitalet, Blegdamsvej, Copenhagen, Denmark. cecilie@nru.dk
authors.forename: Cecilie Löe
authors.initials: CL
authors.lastname: Licht
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017374:Paroxetine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D058828:Serotonin 5-HT4 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D006897:Hydroxyindoleacetic Acid; D017374:Paroxetine; D010880:Piperidines; D012701:Serotonin; D058828:Serotonin 5-HT4 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C107826:RS 67333