Homozygote mice deficient in serotonin 5-HT1B receptor and antidepressant effect of selective serotonin reuptake inhibitors
Trillat AC, Malagie I, Bourin M, Jacquot C, Hen R, Gardier AM.
Laboratoire de Neuropharmacologie EAD MESR 98-213,
Faculte de Pharmacie,
Universite Paris-Sud, Chatenay-Malabry, France.
C R Seances Soc Biol Fil 1998;192(6):1139-47
We use the knockout mice strategy to investigate the contribution of the 5-HT1B receptor in mediating the effects of selective serotonin reuptake inhibitors (SSRI). Using microdialysis in awake 129/Sv mice, we show that the absence of the 5-HT1B receptor in mutant mice (KO 1B -/-) potentiated the effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus, but not in the frontal cortex compared to wild-type mice (WT). Furthermore, using the forced swimming test, we demonstrate that SSRIs decreased immobility of WT mice, and this effect is absent in KO 1B -/- mice showing therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these findings suggest that 5-HT1B autoreceptors limit the effects of SSRI particularly in the hippocampus while postsynaptic 5-HT1B receptors are required for the antidepressant activity of SSRIs.
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