Sub-chronic Administration of Rimonabant Causes Loss of Antidepressive Activity and Decreases Doublecortin Immunoreactivity in the Mouse Hippocampus. Neuroscience letters [Neurosci Lett] Journal article

Rimonabant is a cannabinoid receptor 1 antagonist, and is used to treat anorexia and obesity. However, it has been suggested that rimonabant may act as a depressant. In the present study, we investigated the depressive effects of rimonabant using behavioral and biochemical methods. A single treatment with rimonabant (10mg/kg, p.o) reduced immobility duration in the forced swimming test (FST) to a level similar to that observed for the tricyclic antidepressant, imipramine (15mg/kg, i.p.). However, mice treated with rimonabant for 2 weeks did not show any significant reductions in immobility duration versus vehicle-treated controls. To investigate why the antidepressant effect of rimonabant disappeared after extended treatment, we carried out 5-bromo-2-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry assay. Numbers of BrdU-immunoreactive cells were not significantly changed after administering rimonabant (10mg/kg, p.o) for 2 weeks in the hippocampal dentate gyrus (DG), but interestingly, numbers of DCX-immunopositive cells in the DG were significantly reduced after 2 weeks of rimonabant treatment at doses of 1 or 10mg/kg/day compared with vehicle-treated controls (P < 0.05). These results suggest that sub-chronic treatments with rimonabant inhibit cell proliferation in DG, and that a lack of antidepressive activity may be related to a reduction in cell proliferation in this region.

Neuroscience letters [Neurosci Lett]