Abstract
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 (2 mg 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 2 mg 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 (0.5 mg kg −1) or the 5-HT 2A receptor antagonist MDL 100907 (0.5 mg kg −1). As with citalopram, fluoxetine elevated dialysate 5-HT at both a low (5 mg kg −1) and higher (20 mg 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.
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