DARPP-32: Regulator of the efficacy of dopaminergic neurotransmission

A. A. Fienberg*, N. Hiroi, P. G. Mermelstein, W. J. Song, G. L. Snyder, A. Nishi, A. Cheramy, J. P. O'Callaghan, D. B. Miller, D. G. Cole, 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, J. A. GiraultE. J. Nestler, P. Greengard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

380 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)838-842
Number of pages5
JournalScience
Volume281
Issue number5378
DOIs
StatePublished - Aug 7 1998

ASJC Scopus subject areas

  • General

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