QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 15, 2005, 25(24):5815-5823; doi:10.1523/JNEUROSCI.1120-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (44) Citing Articles via Google Scholar Google Scholar Articles by Kippin, T. E. Articles by van der Kooy, D. Search for Related Content PubMed PubMed Citation Articles by Kippin, T. E. Articles by van der Kooy, D.

 Previous Article  |  Next Article 

Neurobiology of Disease
Dopamine Specifically Inhibits Forebrain Neural Stem Cell Proliferation, Suggesting a Novel Effect of Antipsychotic Drugs

Tod E. Kippin,¹ Shitij Kapur,² and Derek van der Kooy¹

Departments of ¹Medical Genetics and Microbiology and ²Psychiatry, University of Toronto, Toronto, Ontario, Canada M5S 1A8

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.

Key words: haloperidol; proliferation; dopamine receptor; dopamine; neuronal progenitor cell; neurogenesis; stem cells

---

Received Nov 15, 2004; accepted April 27, 2005.

This article has been cited by other articles:

				J. A. Lieberman, F. P. Bymaster, H. Y. Meltzer, A. Y. Deutch, G. E. Duncan, C. E. Marx, J. R. Aprille, D. S. Dwyer, X.-M. Li, S. P. Mahadik, et al. Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection Pharmacol. Rev., September 1, 2008; 60(3): 358 - 403. [Abstract] [Full Text] [PDF]

				M. Mori, J. J. Jefferson, M. Hummel, and D. S. Garbe CNTF: A Putative Link between Dopamine D2 Receptors and Neurogenesis J. Neurosci., June 4, 2008; 28(23): 5867 - 5869. [Full Text] [PDF]

				P. Yang, S. A. Arnold, A. Habas, M. Hetman, and T. Hagg Ciliary Neurotrophic Factor Mediates Dopamine D2 Receptor-Induced CNS Neurogenesis in Adult Mice J. Neurosci., February 27, 2008; 28(9): 2231 - 2241. [Abstract] [Full Text] [PDF]

				M. Geraerts, O. Krylyshkina, Z. Debyser, and V. Baekelandt Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis Stem Cells, February 1, 2007; 25(2): 263 - 270. [Abstract] [Full Text] [PDF]

				A. J. Rashid, C. H. So, M. M. C. Kong, T. Furtak, M. El-Ghundi, R. Cheng, B. F. O'Dowd, and S. R. George D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum PNAS, January 9, 2007; 104(2): 654 - 659. [Abstract] [Full Text] [PDF]

				E. Kim, A. L. Clark, A. Kiss, J. W. Hahn, R. Wesselschmidt, C. J. Coscia, and M. M. Belcheva {micro}- and {kappa}-Opioids Induce the Differentiation of Embryonic Stem Cells to Neural Progenitors J. Biol. Chem., November 3, 2006; 281(44): 33749 - 33760. [Abstract] [Full Text] [PDF]

				C. M. C. Batista, T. E. Kippin, S. Willaime-Morawek, M. K. Shimabukuro, W. Akamatsu, and D. van der Kooy A Progressive and Cell Non-Autonomous Increase in Striatal Neural Stem Cells in the Huntington's Disease R6/2 Mouse J. Neurosci., October 11, 2006; 26(41): 10452 - 10460. [Abstract] [Full Text] [PDF]

				S. Hu, M. C.-J. Cheeran, W. S. Sheng, H. T. Ni, J. R. Lokensgard, and P. K. Peterson Cocaine Alters Proliferation, Migration, and Differentiation of Human Fetal Brain-Derived Neural Precursor Cells J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1280 - 1286. [Abstract] [Full Text] [PDF]

				J. M. Van Kampen and C. B. Eckman Dopamine D3 receptor agonist delivery to a model of Parkinson's disease restores the nigrostriatal pathway and improves locomotor behavior. J. Neurosci., July 5, 2006; 26(27): 7272 - 7280. [Abstract] [Full Text] [PDF]

				N. Freundlieb, C. Francois, D. Tande, W. H. Oertel, E. C. Hirsch, and G. U. Hoglinger Dopaminergic substantia nigra neurons project topographically organized to the subventricular zone and stimulate precursor cell proliferation in aged primates. J. Neurosci., February 22, 2006; 26(8): 2321 - 2325. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help