Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs.

TitleDopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs.
Publication TypeJournal Article
Year of Publication2005
AuthorsKippin TE, Kapur S, van der Kooy D
JournalJ Neurosci
Volume25
Issue24
Pagination5815-23
Date Published2005 Jun 15
ISSN1529-2401
KeywordsAnimals, Antipsychotic Agents, Cell Division, Dopamine, Female, Haloperidol, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Prosencephalon, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D3, Stem Cells
Abstract

Neurogenesis has been implicated in antidepressant drug action and animal models of depression, suggesting that proliferating cells play a role in psychiatric disorders. Similar studies using antipsychotic drugs have yielded conflicting results, perhaps because of the lack of focus on specific cell types. We examine the effect of haloperidol on neural stem cells (NSCs), the ultimate precursors for adult cell genesis. We show that haloperidol increases NSC numbers, resulting in more progenitors and more new neurons and glia in the adult rat brain. The increase in NSCs by haloperidol is dependent on central dopamine D2 receptors, and these receptors are expressed by NSCs. D2 receptor stimulation in vitro inhibits NSC proliferation, which is reversed by haloperidol. Thus, haloperidol increases adult mammalian brain proliferation by antagonizing dopamine at D2 receptors on NSCs. These findings demonstrate a direct link between neural activity and NSC proliferation and implicate cell genesis in antipsychotic drug effects.

DOI10.1523/JNEUROSCI.1120-05.2005
Alternate JournalJ. Neurosci.
PubMed ID15958748