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