PMID- 22827965
OWN - NLM
STAT- MEDLINE
DCOM- 20130821
LR  - 20211021
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 16
IP  - 2
DP  - 2013 Mar
TI  - A physiological role for the dopamine D5 receptor as a regulator of BDNF and Akt 
      signalling in rodent prefrontal cortex.
PG  - 477-83
LID - 10.1017/S1461145712000685 [doi]
AB  - 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-3beta. 
      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.
FAU - Perreault, Melissa L
AU  - Perreault ML
AD  - Centre for Addiction and Mental Health, Toronto, ON, Canada.
FAU - Jones-Tabah, Jace
AU  - Jones-Tabah J
FAU - O'Dowd, Brian F
AU  - O'Dowd BF
FAU - George, Susan R
AU  - George SR
LA  - eng
GR  - R01 DA007223/DA/NIDA NIH HHS/United States
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120725
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Receptors, Dopamine D1)
RN  - 137750-35-7 (Receptors, Dopamine D5)
RN  - 67287-49-4 (2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine)
RN  - 80751-85-5 (SK&F 83959)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 1)
SB  - IM
MH  - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/analogs & 
      derivatives/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dopamine Agonists/pharmacology
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Glutamate Decarboxylase/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D1/deficiency
MH  - Receptors, Dopamine D5/deficiency/*physiology
MH  - Signal Transduction/drug effects/*physiology
PMC - PMC3802523
MID - NIHMS512964
COIS- Statement of Interest: None.
EDAT- 2012/07/26 06:00
MHDA- 2013/08/22 06:00
PMCR- 2013/10/21
CRDT- 2012/07/26 06:00
PHST- 2012/07/26 06:00 [entrez]
PHST- 2012/07/26 06:00 [pubmed]
PHST- 2013/08/22 06:00 [medline]
PHST- 2013/10/21 00:00 [pmc-release]
AID - S1461145712000685 [pii]
AID - 10.1017/S1461145712000685 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2013 Mar;16(2):477-83. doi: 
      10.1017/S1461145712000685. Epub 2012 Jul 25.