Publication Date:
2011-08-13
Description:
Midbrain dopamine neurons regulate many important behavioral processes, and their dysfunctions are associated with several human neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Here, we report that these neurons in mice selectively express guanylyl cyclase-C (GC-C), a membrane receptor previously thought to be expressed mainly in the intestine. GC-C activation potentiates the excitatory responses mediated by glutamate and acetylcholine receptors via the activity of guanosine 3',5'-monophosphate-dependent protein kinase (PKG). Mice in which GC-C has been knocked out exhibit hyperactivity and attention deficits. Moreover, their behavioral phenotypes are reversed by ADHD therapeutics and a PKG activator. These results indicate important behavioral and physiological functions for the GC-C/PKG signaling pathway within the brain and suggest new therapeutic targets for neuropsychiatric disorders related to the malfunctions of midbrain dopamine neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Rong -- Ding, Cheng -- Hu, Ji -- Lu, Yao -- Liu, Fei -- Mann, Elizabeth -- Xu, Fuqiang -- Cohen, Mitchell B -- Luo, Minmin -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1642-6. doi: 10.1126/science.1207675. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21835979" target="_blank"〉PubMed〈/a〉
Keywords:
Amphetamine/administration & dosage
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Animals
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Attention
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Attention Deficit Disorder with Hyperactivity/genetics/*metabolism
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Behavior, Animal/drug effects
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Cyclic GMP/metabolism
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Cyclic GMP-Dependent Protein Kinases/*metabolism
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Disease Models, Animal
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Dopamine/metabolism
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Enzyme Activation
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Gastrointestinal Hormones/metabolism/pharmacology
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Glycine/analogs & derivatives/metabolism/pharmacology
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Impulsive Behavior
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Ligands
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Motor Activity/drug effects
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Natriuretic Peptides/metabolism/pharmacology
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Neurons/*metabolism
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Patch-Clamp Techniques
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Receptors, Glutamate/metabolism
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Receptors, Guanylate Cyclase-Coupled/genetics/*metabolism
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Receptors, Muscarinic/metabolism
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Receptors, Peptide/genetics/*metabolism
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Resorcinols/metabolism/pharmacology
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Signal Transduction
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Substantia Nigra/cytology/*metabolism
;
Ventral Tegmental Area/cytology/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
