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

      Science (New York, N.Y.)

      Amphetamines, pharmacology, Animals, Behavior, Animal, drug effects, Calcium, metabolism, Cocaine, Corpus Striatum, Cyclic AMP-Dependent Protein Kinases, Dopamine, physiology, 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, genetics, Neurons, Phosphoprotein Phosphatases, Phosphoproteins, Phosphorylation, Raclopride, Receptors, Dopamine D1, Receptors, N-Methyl-D-Aspartate, Salicylamides, Sodium-Potassium-Exchanging ATPase, Synaptic Transmission, gamma-Aminobutyric Acid

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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.

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          Journal
          9694658
          10.1126/science.281.5378.838

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