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Recent evidence that 5-HT(2) receptors exert a negative influence on central 5-hydroxytryptamine (5-HT) neurones suggests that 5-HT(2) receptor antagonists may augment the effects of serotonin selective reuptake inhibitors (SSRIs). The present study investigated whether pre-treatment with 5-HT(2) receptor antagonists enhances the effect of SSRI administration on hippocampal extracellular 5-HT of freely moving rats. Administration of the SSRI citalopram at a low (2mg kg(-1)) and higher (4 mg kg(-1)) dose, increased dialysate 5-HT by 5- and 8-fold, respectively. Pre-treatment with the 5-HT(2) receptor antagonist ketanserin (4 mg kg(-1)) augmented the effect of 4 mg kg(-1) but not 2mg kg(-1) citalopram. The effect of 4 mg kg(-1) citalopram was also augmented by pre-treatment with either the 5-HT(2C) receptor antagonist SB 242084 (0.5mg kg(-1)) or the 5-HT(2A) receptor antagonist MDL 100907 (0.5mg kg(-1)). As with citalopram, fluoxetine elevated dialysate 5-HT at both a low (5mg kg(-1)) and higher (20mg kg(-1)) dose. However, neither dose of fluoxetine was augmented by ketanserin (4 mg kg(-1)). These results confirm recent findings that 5-HT(2) receptor antagonists augment the effect of citalopram on extracellular 5-HT, and indicate the involvement of 5-HT(2C) and possibly 5-HT(2A) receptors. The lack of augmentation of fluoxetine might reflect the intrinsic 5-HT(2) receptor antagonist properties of this drug.

Original publication

DOI

10.1016/j.neuropharm.2005.11.020

Type

Journal article

Journal

Neuropharmacology

Publication Date

05/2006

Volume

50

Pages

726 - 732

Keywords

Analysis of Variance, Animals, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Drug Synergism, Hippocampus, Male, Microdialysis, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin 5-HT2 Receptor Antagonists, Serotonin Antagonists, Serotonin Uptake Inhibitors, Wakefulness