PMID- 17559709
OWN - NLM
STAT- MEDLINE
DCOM- 20080415
LR  - 20221207
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 11
IP  - 1
DP  - 2008 Feb
TI  - Brain-derived neurotrophic factor-deficient mice exhibit a hippocampal 
      hyperserotonergic phenotype.
PG  - 79-92
AB  - Growing evidence supports the involvement of brain-derived neurotrophic factor 
      (BDNF) in mood disorders and the mechanism of action of antidepressant drugs. 
      However, the relationship between BDNF and serotonergic signalling is poorly 
      understood. Heterozygous mutants BDNF +/- mice were utilized to investigate the 
      influence of BDNF on the serotonin (5-HT) system and the activity of the 
      serotonin transporter (SERT) in the hippocampus. The zero net flux method of 
      quantitative microdialysis revealed that BDNF +/- heterozygous mice have 
      increased basal extracellular 5-HT levels in the hippocampus and decreased 5-HT 
      reuptake capacity. In keeping with these results, the selective serotonin 
      reuptake inhibitor paroxetine failed to increase hippocampal extracellular 5-HT 
      levels in BDNF +/- mice while it produced robust effects in wild-type 
      littermates. Using in-vitro autoradiography and synaptosome techniques, we 
      investigated the causes of attenuated 5-HT reuptake in BDNF +/- mice. A 
      significant decrease in [3H]citalopram-binding-site density in the CA3 subregion 
      of the ventral hippocampus and a significant reduction in [3H]5-HT uptake in 
      hippocampal synaptosomes, revealed mainly a decrease in SERT function. However, 
      5-HT1A autoreceptors were not desensitized in BDNF +/- mice. These results 
      provide evidence that constitutive reductions in BDNF modulate SERT function 
      reuptake in the hippocampus.
FAU - Guiard, Bruno P
AU  - Guiard BP
AD  - Universite Paris-Sud, EA3544, Faculte de Pharmacie, Chatenay-Malabry, France.
FAU - David, Denis J P
AU  - David DJ
FAU - Deltheil, Thierry
AU  - Deltheil T
FAU - Chenu, Franck
AU  - Chenu F
FAU - Le Maitre, Erwan
AU  - Le Maitre E
FAU - Renoir, Thibault
AU  - Renoir T
FAU - Leroux-Nicollet, Isabelle
AU  - Leroux-Nicollet I
FAU - Sokoloff, Pierre
AU  - Sokoloff P
FAU - Lanfumey, Laurence
AU  - Lanfumey L
FAU - Hamon, Michel
AU  - Hamon M
FAU - Andrews, Anne M
AU  - Andrews AM
FAU - Hen, Rene
AU  - Hen R
FAU - Gardier, Alain M
AU  - Gardier AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070611
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0DHU5B8D6V (Citalopram)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 333DO1RDJY (Serotonin)
RN  - 41VRH5220H (Paroxetine)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
MH  - Animals
MH  - Autoradiography
MH  - Brain Chemistry/drug effects
MH  - Brain-Derived Neurotrophic Factor/*deficiency/*genetics
MH  - Citalopram
MH  - Dose-Response Relationship, Drug
MH  - Electrophysiology
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microdialysis
MH  - Paroxetine
MH  - Phenotype
MH  - Raphe Nuclei/drug effects/metabolism
MH  - Receptor, Serotonin, 5-HT1A/drug effects/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors
MH  - Synaptic Transmission/genetics/physiology
EDAT- 2007/06/15 09:00
MHDA- 2008/04/16 09:00
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2008/04/16 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
AID - S1461145707007857 [pii]
AID - 10.1017/S1461145707007857 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2008 Feb;11(1):79-92. doi: 10.1017/S1461145707007857. 
      Epub 2007 Jun 11.