TY - JOUR
T1 - Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus
AU - Halim, Nader D.
AU - Weickert, Cynthia Shannon
AU - McClintock, Benjamin W.
AU - Weinberger, Daniel R.
AU - Lipska, Barbara K.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection.
AB - It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection.
KW - Antipsychotic
KW - BrdU
KW - Dentate gyrus
KW - Neuroleptic
KW - Schizophrenia
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UR - http://www.scopus.com/inward/citedby.url?scp=2442691413&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300422
DO - 10.1038/sj.npp.1300422
M3 - Article
C2 - 15010699
AN - SCOPUS:2442691413
SN - 0893-133X
VL - 29
SP - 1063
EP - 1069
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 6
ER -