Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.

Wang HD, Dunnavant FD, Jarman T, Deutch AY
Neuropsychopharmacology. 2004 29 (7): 1230-8

PMID: 15085089 · DOI:10.1038/sj.npp.1300449

The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.

Copyright 2004 Nature Publishing Group

MeSH Terms (18)

Analysis of Variance Animals Antipsychotic Agents Benzodiazepines Bromodeoxyuridine Cell Count Cell Division Corpus Striatum Dentate Gyrus Haloperidol Immunohistochemistry Male Neurons Olanzapine Phosphopyruvate Hydratase Prosencephalon Rats Rats, Sprague-Dawley

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