PMID- 17327885
OWN - NLM
STAT- MEDLINE
DCOM- 20080109
LR  - 20221207
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 32
IP  - 11
DP  - 2007 Nov
TI  - Chronic duloxetine treatment induces specific changes in the expression of BDNF 
      transcripts and in the subcellular localization of the neurotrophin protein.
PG  - 2351-9
AB  - There is growing evidence that brain-derived neurotrophic factor (BDNF) can be 
      relevant to mood disorders and that modulation of its biosynthesis following 
      prolonged antidepressant treatment may contribute to neuroplastic changes 
      required for clinical response. In the present study, we investigated the effects 
      of the novel antidepressant duloxetine on BDNF in the rat brain. Duloxetine is a 
      serotonin-norepinephrine reuptake inhibitor that differs from other 
      antidepressants by virtue of its balanced potency on both neurotransmitter 
      systems. We found that chronic, but not acute, treatment with duloxetine produces 
      a robust increase of exon V BDNF mRNA levels in frontal cortex when the animals 
      were killed 1 or 24 h after the last administration. The expression of the 
      neurotrophin was also increased in other cortical subregions, but not in the 
      hippocampus. We also found that the increased expression of BDNF in frontal 
      cortex was mainly sustained by enhanced mRNA levels for exons I and III, whereas 
      the expression of exon IV was reduced. Protein analysis in different subcellular 
      fractions showed that chronic treatment with duloxetine, but not with the 
      prototypical SSRI fluoxetine, reduced mature BDNF in the cytosol, but markedly 
      increased its levels in the crude synaptosomal fraction. Our data suggest that 
      chronic treatment with the novel antidepressant duloxetine not only produces a 
      marked upregulation of BDNF mRNA and protein, but may also affect the subcellular 
      redistribution of the neurotrophin. These changes might improve synaptic 
      plasticity and cognitive function that are defective in depressed subjects.
FAU - Calabrese, Francesca
AU  - Calabrese F
AD  - Department of Pharmacological Sciences, Center of Neuropharmacology, University 
      of Milan, Milan, Italy.
FAU - Molteni, Raffaella
AU  - Molteni R
FAU - Maj, Paola F
AU  - Maj PF
FAU - Cattaneo, Annamaria
AU  - Cattaneo A
FAU - Gennarelli, Massimo
AU  - Gennarelli M
FAU - Racagni, Giorgio
AU  - Racagni G
FAU - Riva, Marco A
AU  - Riva MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070228
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (Thiophenes)
RN  - 9044SC542W (Duloxetine Hydrochloride)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Drug Administration Schedule
MH  - Duloxetine Hydrochloride
MH  - Electrophoretic Mobility Shift Assay
MH  - Exons
MH  - Gene Expression Regulation/*drug effects
MH  - Male
MH  - Prefrontal Cortex/drug effects/*ultrastructure
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Selective Serotonin Reuptake Inhibitors/*administration & dosage
MH  - Subcellular Fractions/drug effects/metabolism
MH  - Thiophenes/*administration & dosage
MH  - Time Factors
EDAT- 2007/03/01 09:00
MHDA- 2008/01/10 09:00
CRDT- 2007/03/01 09:00
PHST- 2007/03/01 09:00 [pubmed]
PHST- 2008/01/10 09:00 [medline]
PHST- 2007/03/01 09:00 [entrez]
AID - 1301360 [pii]
AID - 10.1038/sj.npp.1301360 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2007 Nov;32(11):2351-9. doi: 10.1038/sj.npp.1301360. 
      Epub 2007 Feb 28.