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DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission

Science  07 Aug 1998:
Vol. 281, Issue 5378, pp. 838-842
DOI: 10.1126/science.281.5378.838

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Abstract

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.

  • * To whom correspondence should be addressed. E-mail: fienba{at}rockvax.rockefeller.edu

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

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

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

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

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