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DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.

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.

Pubmed ID: 9694658

Authors

  • Fienberg AA
  • Hiroi N
  • Mermelstein PG
  • Song W
  • Snyder GL
  • Nishi A
  • Cheramy A
  • O'Callaghan JP
  • Miller DB
  • Cole DG
  • Corbett R
  • Haile CN
  • Cooper DC
  • Onn SP
  • Grace AA
  • Ouimet CC
  • White FJ
  • Hyman SE
  • Surmeier DJ
  • Girault J
  • Nestler EJ
  • Greengard P

Journal

Science (New York, N.Y.)

Publication Data

August 7, 1998

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA 08227
  • Agency: NIDA NIH HHS, Id: DA10044
  • Agency: NIDA NIH HHS, Id: F31 DA005794
  • Agency: NIMH NIH HHS, Id: MH40899

Mesh Terms

  • Amphetamines
  • Animals
  • Behavior, Animal
  • Calcium
  • Cocaine
  • Corpus Striatum
  • Cyclic AMP-Dependent Protein Kinases
  • Dopamine
  • Dopamine Agents
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Female
  • Gene Expression Regulation
  • Gene Targeting
  • Genes, fos
  • Glutamic Acid
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Neurons
  • Phosphoprotein Phosphatases
  • Phosphoproteins
  • Phosphorylation
  • Raclopride
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • Salicylamides
  • Sodium-Potassium-Exchanging ATPase
  • Synaptic Transmission
  • gamma-Aminobutyric Acid