PMID- 25744957
OWN - NLM
STAT- MEDLINE
DCOM- 20160622
LR  - 20181202
IS  - 1469-994X (Electronic)
IS  - 1462-2203 (Print)
IS  - 1462-2203 (Linking)
VI  - 17
IP  - 12
DP  - 2015 Dec
TI  - Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following 
      Nicotine Withdrawal in Mice.
PG  - 1428-35
LID - 10.1093/ntr/ntv047 [doi]
AB  - INTRODUCTION: Nicotine withdrawal is characterized by both affective and 
      cognitive symptoms. Identifying genetic polymorphisms that could affect the 
      symptoms associated with nicotine withdrawal are important in predicting 
      withdrawal sensitivity and identifying personalized cessation therapies. In the 
      current study we used a mouse model of a non-synonymous single nucleotide 
      polymorphism in the translated region of the brain-derived neurotrophic factor 
      (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid 
      (Val66Met) to examine the relationship between the Val66Met single nucleotide 
      polymorphism and nicotine dependence. METHODS: This study measured proBDNF and 
      the BDNF prodomain levels following nicotine and nicotine withdrawal and examined 
      a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three 
      behavioral paradigms: novelty-induced hypophagia, marble burying, and the 
      open-field test. RESULTS: Using the BDNF knock-in mouse containing the BDNF 
      Val66Met polymorphism we found: (1) blunted anxiety-like behavior in 
      BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: 
      novelty-induced hypophagia, marble burying, and the open-field test; (2) the 
      anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) 
      an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine 
      withdrawal. CONCLUSIONS: Our study is the first to examine the effect of the BDNF 
      Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in 
      mice. In these mice, a single-nucleotide polymorphism in the translated region of 
      the BDNF gene can result in a blunted withdrawal, as measured by decreased 
      anxiety-like behavior. The significant increase in the BDNF prodomain in 
      BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this 
      ligand in the circuitry remodeling after withdrawal.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the Society 
      for Research on Nicotine and Tobacco. All rights reserved. For permissions, 
      please e-mail: journals.permissions@oup.com.
FAU - Lee, Bridgin G
AU  - Lee BG
AD  - Department of Pharmacology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA;
FAU - Anastasia, Agustin
AU  - Anastasia A
AD  - Department of Medicine, Weill Cornell Medical College of Cornell University, New 
      York, NY;
FAU - Hempstead, Barbara L
AU  - Hempstead BL
AD  - Department of Medicine, Weill Cornell Medical College of Cornell University, New 
      York, NY;
FAU - Lee, Francis S
AU  - Lee FS
AD  - Department of Psychiatry, Weill Cornell Medical College of Cornell University, 
      New York, NY.
FAU - Blendy, Julie A
AU  - Blendy JA
AD  - Department of Pharmacology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA; blendy@mail.med.upenn.edu.
LA  - eng
GR  - T32 GM-008076/GM/NIGMS NIH HHS/United States
GR  - R01NS030687/NS/NINDS NIH HHS/United States
GR  - T32 GM008076/GM/NIGMS NIH HHS/United States
GR  - P50-CA143187/CA/NCI NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150305
PL  - England
TA  - Nicotine Tob Res
JT  - Nicotine & tobacco research : official journal of the Society for Research on 
      Nicotine and Tobacco
JID - 9815751
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 6M3C89ZY6R (Nicotine)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Animals
MH  - Anxiety/*genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Female
MH  - Gene Knock-In Techniques
MH  - Male
MH  - Methionine/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Nicotine/*administration & dosage
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Substance Withdrawal Syndrome/*genetics/psychology
MH  - Tobacco Use Disorder/genetics/psychology
MH  - Valine/*genetics
PMC - PMC4654761
EDAT- 2015/03/07 06:00
MHDA- 2016/06/23 06:00
PMCR- 2016/12/01
CRDT- 2015/03/07 06:00
PHST- 2014/07/16 00:00 [received]
PHST- 2015/02/16 00:00 [accepted]
PHST- 2015/03/07 06:00 [entrez]
PHST- 2015/03/07 06:00 [pubmed]
PHST- 2016/06/23 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - ntv047 [pii]
AID - 10.1093/ntr/ntv047 [doi]
PST - ppublish
SO  - Nicotine Tob Res. 2015 Dec;17(12):1428-35. doi: 10.1093/ntr/ntv047. Epub 2015 Mar 
      5.