"Antidepressant-like" phenotype in mice lacking the 5-HT2B receptor

DIAZ SL; NARBOUX-NÊME N; DOLY S; MAROTEAUX L

Heidelberg

Workshop; EMBL Workshop on Translating Behaviour: Bridging Clinical and Animal Model Research; 2009

European Molecular Biology Laboratory (EMBL)

The 5-HT2B receptor has been recently implicated in the modulation of the activity of the serotonin transporter, a target of some antidepressant drugs. Given the interaction between serotonin and depression, we analyzed the behavioral and biochemical profile in a mice model where the 5-HT2B receptor is knocked-out (5-HT2BKO). Adult male and female 5-HT2BKO and their 129/SvPAS control mice were used. In the novelty-suppressed feeding test, classically employed for evaluating chronic effects of antidepressants, the basal response of 5-HT2BKOmice was similar to that of control mice chronically treated with antidepressants. The forced swimming test, a test for screening potential-antidepressant drugs, revealed no basal differences in the immobility time between control and 5-HT2BKO mice. However, these mutant mice were not able to respond to SSRI antidepressants in this test. Anhedonia-like behavior was also studied by measuring sucrose consumption: 5-HT2BKO mice significantly consumed more sucrose than control mice, a typical response of chronically antidepressant-treated animals. This behavioral profile was as well associated to a higher basal expression of hippocampal brain-derived neurotrophic factor (BDNF) in 5-HT2BKO mice. Decreased levels of BDNF have been correlated with a depression-like phenotype in mice. In addition, most of antidepressant treatments induce an increased expression of this neurotrophin in the hippocampus. Finally, an increase of BDNF levels was induced in wild type mice by acute ketamine administration, but on the contrary, basal levels of BDNF in 5-HT2BKO mice could not been further increased after ketamine. Altogether, these observations suggest that the genetic ablation of the 5-HT2B receptor induces an "antidepressant-like" phenotype which could partially be determined by a basal overexpression of BDNF in the hippocampus.