Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.
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.
Wang
Hui-Dong
HD
Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212, USA. huidong.wang@vanderbilt.edu
Dunnavant
Floyd D
FD
Jarman
Tabitha
T
Deutch
Ariel Y
AY
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D000077152:Olanzapine; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D006220:Haloperidol; D000077152:Olanzapine