Antidepressants alter cell proliferation in the adult brain in vivo and inneural cultures in vitro

The action of antidepressants on cell proliferation (bromodeoxyuridine (Brd U) or [H-3]thymidine incorporation} was studied in the adult rat hippocampu s in vivo and in neural precursors (immature rat cerebellar granule cells) in vitro. In vivo, prolonged (21 days) but not acute (single) intraperitone al treatment with fluoxetine (5 mg/kg) resulted in a 3.4-fold increase of b romodeoxyuridine-positive cells in the subgranular zone of the dentate gyru s. In cell cultures, at 1 and 10 days in vitro, 48-h fluoxetine exposure (1 muM. which is comparable to therapeutic plasma concentrations) reduced thy midine incorporation when initiated at 1 day in vitro, but increased cell p roliferation when initiated at 10 days in vitro. Clomipramine and imipramin e produced similar action in vitro; desipramine was ineffective. (C) 2001 E lsevier Science B.V. All rights reserved.