Effects of the 5-HT(4) receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels
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Effects of the 5-HT(4) receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels. / Licht, Cecilie Löe; Knudsen, Gitte Moos; Sharp, Trevor.
In: Neuroscience Letters, Vol. 476, No. 2, 31.05.2010, p. 58-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of the 5-HT(4) receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels
AU - Licht, Cecilie Löe
AU - Knudsen, Gitte Moos
AU - Sharp, Trevor
N1 - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
PY - 2010/5/31
Y1 - 2010/5/31
N2 - 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.
AB - 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.
KW - Aniline Compounds
KW - Animals
KW - Drug Synergism
KW - Extracellular Space
KW - Hippocampus
KW - Hydroxyindoleacetic Acid
KW - Male
KW - Microdialysis
KW - Paroxetine
KW - Piperidines
KW - Rats
KW - Rats, Sprague-Dawley
KW - Serotonin
KW - Serotonin 5-HT4 Receptor Agonists
KW - Serotonin Uptake Inhibitors
U2 - 10.1016/j.neulet.2010.04.002
DO - 10.1016/j.neulet.2010.04.002
M3 - Journal article
C2 - 20381585
VL - 476
SP - 58
EP - 61
JO - Neuroscience letters. Supplement
JF - Neuroscience letters. Supplement
SN - 0167-6253
IS - 2
ER -
ID: 34142880