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Science 7 August 1998:
Vol. 281. no. 5378, pp. 838 - 842
DOI: 10.1126/science.281.5378.838
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Reports

DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission

A. A. Fienberg, * N. Hiroi, dagger P. G. Mermelstein, W.-J. Song, G. L. Snyder, A. Nishi, A. Cheramy, J. P. O'Callaghan, D. B. Miller, D. G. Cole, ddagger R. Corbett, C. N. Haile, D. C. Cooper, S. P. Onn, A. A. Grace, C. C. Ouimet, F. J. White, S. E. Hyman, § D. J. Surmeier, parallel J.-A. Girault, E. J. Nestler, P. Greengard

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.

A. A. Fienberg, G. L. Snyder, A. Nishi, P. Greengard, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA. N. Hiroi, C. N. Haile, E. J. Nestler, Laboratory of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, CT 06508, USA. P. G. Mermelstein, W.-J. Song, D. J. Surmeier, Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, TN 38163, USA. A. Cheramy and J. A. Girault, INSERM U114, College de France, 75005 Paris, France. J. P. O'Callaghan and D. B. Miller, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. D. G. Cole and S. E. Hyman, Molecular and Developmental Neuroscience and Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. R. Corbett, Hoechst Marion Roussel, Inc., Somerville, NJ 08807, USA. D. C. Cooper and F. J. White, Department of Neuroscience, Chicago Medical School, North Chicago, IL 60064, USA. S. P. Onn and A. A. Grace, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. C. C. Ouimet, Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
*   To whom correspondence should be addressed. E-mail: fienba{at}rockvax.rockefeller.edu

dagger    Present address: Laboratory of Molecular Psychobiology, Departments of Psychiatry and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

ddagger    Present address: Vertex Pharmaceuticals, Cambridge, MA 02139, USA.

§   Present address: Office of the Director, National Institute of Mental Health, Bethesda, MD 20892, USA.

parallel    Present address: Department of Physiology, NUIN, Northwestern University School of Medicine, Chicago, IL 60611, USA.

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