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.
Fienberg
A A
AA
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.
Hiroi
N
N
Mermelstein
P G
PG
Song
W
W
Snyder
G L
GL
Nishi
A
A
Cheramy
A
A
O'Callaghan
J P
JP
Miller
D B
DB
Cole
D G
DG
Corbett
R
R
Haile
C N
CN
Cooper
D C
DC
Onn
S P
SP
Grace
A A
AA
Ouimet
C C
CC
White
F J
FJ
Hyman
S E
SE
Surmeier
D J
DJ
Girault
J
J
Nestler
E J
EJ
Greengard
P
P
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D016762:Genes, fos; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010750:Phosphoproteins; D010766:Phosphorylation; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012457:Salicylamides / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000662:Amphetamines; D015259:Dopamine Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; D018698:Glutamic Acid; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D003042:Cocaine; D002118:Calcium; D004298:Dopamine