PMID- 15381288
OWN - NLM
STAT- MEDLINE
DCOM- 20050304
LR  - 20221207
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 128
IP  - 3
DP  - 2004
TI  - Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic 
      factor varies depending on length of treatment.
PG  - 597-604
AB  - Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be 
      implicated in the clinical action of antidepressant drugs. Repeated (2-3 weeks) 
      administration of antidepressant drugs increases BDNF gene expression. The onset 
      of this response as well as concomitant effects on the corresponding BDNF protein 
      is however, unclear. The present study investigated the effects of acute and 
      chronic administration of the selective serotonin reuptake inhibitor, fluoxetine 
      (10mg/kg p.o.), upon regional rat brain levels of BDNF mRNA and protein 
      expression. To improve the clinical significance of the study, fluoxetine was 
      administered orally and mRNA and protein levels were determined ex vivo using the 
      techniques of in situ hybridisation histochemistry and immunocytochemistry 
      respectively. Direct measurement of BDNF protein was also carried out using 
      enzyme-linked immunosorbent assay (ELISA). Four days of once daily oral 
      administration of fluoxetine induced decreases in BDNF mRNA (hippocampus, medial 
      habenular and paraventricular thalamic nuclei). Whilst 7 days of treatment showed 
      a non-significant increase in BDNF mRNA, there were marked and region-specific 
      increases following 14 days of treatment. BDNF protein levels remained unaltered 
      until 21 days of fluoxetine treatment, when the numbers of BDNF immunoreactive 
      cells were increased, reaching significance in the pyramidal cell layer of CA1 
      and CA3 regions of Ammon's horn (CA1 and CA3) but not in the other sub-regions of 
      the hippocampus. Indicative of the highly regional change within the hippocampus, 
      the ELISA method failed to demonstrate significant up-regulation at 21 days, 
      measuring levels of BDNF protein in the whole hippocampus. In contrast to the 
      detected time dependent and biphasic response of the BDNF gene, 
      activity-regulated, cytoskeletal-associated protein (Arc) mRNA showed a gradual 
      increase during the 14-day course of treatment. The results presented here show 
      that BDNF is expressed differentially depending on length of fluoxetine 
      administration, which could contribute in explaining the slow onset of 
      antidepressant activity observed with selective serotonin reuptake inhibitors.
FAU - De Foubert, G
AU  - De Foubert G
AD  - Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort 
      University, The Gateway, Leicester, LE1 9BH, UK.
FAU - Carney, S L
AU  - Carney SL
FAU - Robinson, C S
AU  - Robinson CS
FAU - Destexhe, E J
AU  - Destexhe EJ
FAU - Tomlinson, R
AU  - Tomlinson R
FAU - Hicks, C A
AU  - Hicks CA
FAU - Murray, T K
AU  - Murray TK
FAU - Gaillard, J P
AU  - Gaillard JP
FAU - Deville, C
AU  - Deville C
FAU - Xhenseval, V
AU  - Xhenseval V
FAU - Thomas, C E
AU  - Thomas CE
FAU - O'Neill, M J
AU  - O'Neill MJ
FAU - Zetterstrom, T S C
AU  - Zetterstrom TS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/*metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/drug effects/genetics/*metabolism
MH  - Cytoskeletal Proteins/genetics
MH  - Depressive Disorder/*drug therapy/*metabolism/physiopathology
MH  - Down-Regulation/drug effects/physiology
MH  - Drug Administration Schedule
MH  - Fluoxetine/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Nerve Tissue Proteins/genetics
MH  - Pyramidal Cells/drug effects/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time/drug effects/physiology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - Time Factors
EDAT- 2004/09/24 05:00
MHDA- 2005/03/05 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/06/24 00:00 [accepted]
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2005/03/05 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - S0306-4522(04)00536-6 [pii]
AID - 10.1016/j.neuroscience.2004.06.054 [doi]
PST - ppublish
SO  - Neuroscience. 2004;128(3):597-604. doi: 10.1016/j.neuroscience.2004.06.054.