Publication Date:
1998-08-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fienberg, A A -- Hiroi, N -- Mermelstein, P G -- Song, W -- Snyder, G L -- Nishi, A -- Cheramy, A -- O'Callaghan, J P -- Miller, D B -- Cole, D G -- Corbett, R -- Haile, C N -- Cooper, D C -- Onn, S P -- Grace, A A -- Ouimet, C C -- White, F J -- Hyman, S E -- Surmeier, D J -- Girault, J -- Nestler, E J -- Greengard, P -- DA 08227/DA/NIDA NIH HHS/ -- DA10044/DA/NIDA NIH HHS/ -- F31 DA005794/DA/NIDA NIH HHS/ -- MH40899/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 7;281(5378):838-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9694658" target="_blank"〉PubMed〈/a〉
Keywords:
Amphetamines/pharmacology
;
Animals
;
Behavior, Animal/drug effects
;
Calcium/metabolism
;
Cocaine/pharmacology
;
Corpus Striatum/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Dopamine/pharmacology/*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/*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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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