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.
BACKGROUND
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.


OBJECTIVE
This study examined the role of multiple classes of 5-HT receptor in citalopram-induced LA.


METHODS
The most selective antagonists currently available were used.


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.


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.
Millan
Mark J
MJ
Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290 Croissy/Seine, France. mark.millan@fr.netgrs.com
Veiga
Sylvie
S
Girardon
Sylvie
S
Brocco
Mauricette
M
D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004779:Environment Design; D016666:Fluvoxamine / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009069:Movement Disorders / Q000517:prevention & control*; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000502:physiology; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D015283:Citalopram; D016666:Fluvoxamine; D044302:Receptor, Serotonin, 5-HT1B; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors