Document Detail


A physiological role for the dopamine D5 receptor as a regulator of BDNF and Akt signalling in rodent prefrontal cortex.
MedLine Citation:
PMID:  22827965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dopamine D5 receptor (D5R) exhibits a wide distribution in prefrontal cortex (PFC) but its role in this region has not yet been elucidated. In the present study, we identified a novel physiological function for the D(5)R as a regulator of brain-derived neurotrophic factor (BDNF) and Akt signalling in PFC. Specifically, acute activation of the D(5)R by the dopamine agonist SKF 83959 enhanced BDNF expression and signalling through its receptor, tropomyosin receptor kinase B (TrkB), in rats and in mice gene-deleted for the D1 receptor but not the D(5)R. These changes were concomitant with increased expression of GAD67, a protein whose down-regulation has been implicated in the aetiology of schizophrenia. Furthermore, D(5)R activation increased phosphorylation of Akt at the Ser(473) site, consequently decreasing the activity of its substrate GSK-3β. These findings could have wide-reaching implications given evidence showing activation of these pathways in PFC has therapeutic effects in neuropsychiatric disorders such as drug addiction, schizophrenia and depression.
Authors:
Melissa L Perreault; Jace Jones-Tabah; Brian F O'Dowd; Susan R George
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-25
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  16     ISSN:  1469-5111     ISO Abbreviation:  Int. J. Neuropsychopharmacol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-08-21     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  477-83     Citation Subset:  IM    
Affiliation:
Centre for Addiction and Mental Health, Toronto, ON, Canada.
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MeSH Terms
Descriptor/Qualifier:
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives,  pharmacology
Analysis of Variance
Animals
Brain-Derived Neurotrophic Factor / metabolism*
Dopamine Agonists / pharmacology
Gene Expression Regulation / drug effects,  genetics
Glutamate Decarboxylase / metabolism
Glycogen Synthase Kinase 3 / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase Type II / metabolism
Prefrontal Cortex / drug effects,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 / deficiency
Receptors, Dopamine D5 / deficiency,  physiology*
Signal Transduction / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
R01 DA007223/DA/NIDA NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Dopamine Agonists; 0/Receptors, Dopamine D1; 137750-35-7/Receptors, Dopamine D5; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 80751-85-5/SK&F 83959; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1
Comments/Corrections

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