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Blockade of serotonin 5-HT1B and 5-HT2A receptors suppresses the induction of locomotor activity by 5-HT reuptake inhibitors, citalopram and fluvoxamine, in NMRI mice exposed to a novel environment: a comparison to other 5-HT receptor subtypes.
- Source :
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Psychopharmacology [Psychopharmacology (Berl)] 2003 Aug; Vol. 168 (4), pp. 397-409. Date of Electronic Publication: 2003 Apr 30. - Publication Year :
- 2003
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Abstract
- Rationale: Though 5-HT plays an important role in the modulation of motor function, which is perturbed in depressive states, little is known concerning the influence of serotonin reuptake inhibitors (SSRIs) on locomotor activity (LA). Recently, we demonstrated that SSRIs, such as citalopram, enhance LA in mice exposed to a novel environment.<br />Objectives: This study examined the role of multiple classes of 5-HT receptor in citalopram-induced LA.<br />Methods: The most selective antagonists currently available were used.<br />Results: Citalopram-induced LA was dose-dependently attenuated by the 5-HT1B/1D receptor antagonists, S18127, GR125,743 and GR127,935, and by the selective 5-HT1B antagonist, SB224,289, but unaffected by the selective 5-HT1A antagonist, WAY100,635. The selective antagonists at 5-HT2A receptors, MDL100,907 and SR46,349 also dose-dependently attenuated induction of locomotion by citalopram, whereas the 5-HT2B antagonist, SB204,741, and the 5-HT2B/2C antagonist, SB206,553 were ineffective. Further, the selective 5-HT2C antagonist, SB242,084, potentiated the response to citalopram. Selective antagonists at 5-HT3 (ondansetron), 5-HT4 (GR125,487), 5-HT6 (SB271,046) and 5-HT7 (SB269,970) receptors did not significantly modify the action of citalopram. Underpinning these findings, SB224,289, GR125,743, MDL100,907 and SR46,349 likewise attenuated induction of locomotion by a further SSRI, fluvoxamine.<br />Conclusions: The locomotor response to SSRIs of mice exposed to a novel environment is mediated via 5-HT1B and 5-HT2A receptors. In view of the importance of motor function to the etiology and treatment of depression, the significance of these observations to the clinical actions of SSRIs will be of interest to elucidate.
- Subjects :
- Animals
Environment Design
Injections, Subcutaneous
Male
Mice
Receptor, Serotonin, 5-HT1B drug effects
Receptor, Serotonin, 5-HT1B physiology
Receptor, Serotonin, 5-HT2B drug effects
Receptor, Serotonin, 5-HT2B physiology
Citalopram pharmacology
Fluvoxamine pharmacology
Motor Activity drug effects
Movement Disorders prevention & control
Receptors, Serotonin classification
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Selective Serotonin Reuptake Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0033-3158
- Volume :
- 168
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12721776
- Full Text :
- https://doi.org/10.1007/s00213-003-1389-y