Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro.
The action of antidepressants on cell proliferation (bromodeoxyuridine (BrdU) or [3H]thymidine incorporation) was studied in the adult rat hippocampus in vivo and in neural precursors (immature rat cerebellar granule cells) in vitro. In vivo, prolonged (21 days) but not acute (single) intraperitoneal treatment with fluoxetine (5 mg/kg) resulted in a 3.4-fold increase of bromodeoxyuridine-positive cells in the subgranular zone of the dentate gyrus. In cell cultures, at 1 and 10 days in vitro, 48-h fluoxetine exposure (1 microM, which is comparable to therapeutic plasma concentrations) reduced thymidine incorporation when initiated at 1 day in vitro, but increased cell proliferation when initiated at 10 days in vitro. Clomipramine and imipramine produced similar action in vitro; desipramine was ineffective.
Manev
H
H
Department of Psychiatry, The Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor Street MC912, 60612, Chicago, IL, USA. HManev@psych.uic.edu
Uz
T
T
Smalheiser
N R
NR
Manev
R
R
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D009420:Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D000928:Antidepressive Agents; D005473:Fluoxetine; D002997:Clomipramine; D007099:Imipramine; D003891:Desipramine; D013936:Thymidine