DARPP-32: regulator of the efficacy of dopaminergic neurotransmission

Science. 1998 Aug 7;281(5378):838-42. doi: 10.1126/science.281.5378.838.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Amphetamines
  • Dopamine Agents
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • Salicylamides
  • Glutamic Acid
  • Raclopride
  • gamma-Aminobutyric Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Sodium-Potassium-Exchanging ATPase
  • Cocaine
  • Calcium
  • Dopamine