1. DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission
- Author
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Paul Greengard, Noboru Hiroi, D. J. Surmeier, Wen Jie Song, Anthony A. Grace, James P. O'Callaghan, Douglas G. Cole, Charles C. Ouimet, Allen A. Fienberg, F. J. White, S. P. Onn, Eric J. Nestler, R. Corbett, Gretchen L. Snyder, D. B. Miller, Steven E. Hyman, Colin N. Haile, Paul G. Mermelstein, Donald C. Cooper, Jean-Antoine Girault, Akinori Nishi, and A. Cheramy
- Subjects
Male ,Dopamine and cAMP-Regulated Phosphoprotein 32 ,medicine.medical_specialty ,Dopamine ,Dopamine Agents ,Glutamic Acid ,Nerve Tissue Proteins ,Neurotransmission ,Biology ,Pharmacology ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Mice ,chemistry.chemical_compound ,Cocaine ,Internal medicine ,Salicylamides ,Phosphoprotein Phosphatases ,medicine ,Animals ,Phosphorylation ,Neurotransmitter ,gamma-Aminobutyric Acid ,Neurons ,Raclopride ,Multidisciplinary ,Behavior, Animal ,Receptors, Dopamine D1 ,Amphetamines ,Dopaminergic ,Genes, fos ,Phosphoproteins ,Cyclic AMP-Dependent Protein Kinases ,Adenosine ,Corpus Striatum ,Mice, Inbred C57BL ,PPP1R1B ,Endocrinology ,Gene Expression Regulation ,chemistry ,Gene Targeting ,Forebrain ,Calcium ,Female ,Sodium-Potassium-Exchanging ATPase ,medicine.drug - 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.
- Published
- 1998
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