5-HT1B serotonin receptors and antidepressant
effects of selective serotonin reuptake

by
Gardier AM, Trillat AC, Malagie I, David D, Hascoet M,
Colombel MC, Jolliet P, Jacquot C, Hen R, Bourin M.
Laboratoire de neuropharmacologie Upres EAD MENRT,
institut de signalisation et d'innovation therapeutique (IFR75),
faculte de pharmacie, universite Paris-Sud,
Chatenay-Malabry, France.
alain.gardier@cep.u-psud.fr
C R Acad Sci III 2001 May; 324(5):433-41


ABSTRACT

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 5-HT1B receptor subtype in mediating the effects of selective serotonin reuptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg dose but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiates the effect of a single administration of paroxetine on [5-HT]ext more in the ventral hippocampus than in the frontal cortex. Furthermore, we demonstrate that SSRIs decrease immobility in the forced swimming test; this effect is absent in 5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant activity of SSRIs.
P11
SSRIs
5-HT1
5-HT2
5-HT3
5-HT1a
5-HT2c
Anpirtoline
Eltoprazine
Zolmitriptan
Knockout mice
5-HT2c/5-HT2b
5-HT1a v 5-HT1b
MDMA and 5-HT1a
5-HT1b and reward
5-HT1b and anxiety
5-HT1b and aggression
Aggression and serotonin
5-HT-moduline, serotonin and mood
5-HT7 receptor antagonists as antidepressants
Depression, SSRIs and the serotonin 5-HT2 receptors


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