PMID- 23042896
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20220309
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 338
IP  - 6103
DP  - 2012 Oct 5
TI  - BDNF is a negative modulator of morphine action.
PG  - 124-8
LID - 10.1126/science.1222265 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural 
      plasticity, promoting, for example, the actions of stimulant drugs of abuse such 
      as cocaine. We discovered a surprising opposite role for BDNF in countering 
      responses to chronic morphine exposure. The suppression of BDNF in the ventral 
      tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) 
      neuron excitability and promote reward. In contrast, optical stimulation of VTA 
      DA terminals in nucleus accumbens (NAc) completely reversed the suppressive 
      effect of BDNF on morphine reward. Furthermore, we identified numerous genes in 
      the NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the 
      context of chronic morphine exposure mediated this counteractive function. These 
      findings provide insight into the molecular basis of morphine-induced 
      neuroadaptations in the brain's reward circuitry.
FAU - Koo, Ja Wook
AU  - Koo JW
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai 
      School of Medicine, New York, NY 10029, USA.
FAU - Mazei-Robison, Michelle S
AU  - Mazei-Robison MS
FAU - Chaudhury, Dipesh
AU  - Chaudhury D
FAU - Juarez, Barbara
AU  - Juarez B
FAU - LaPlant, Quincey
AU  - LaPlant Q
FAU - Ferguson, Deveroux
AU  - Ferguson D
FAU - Feng, Jian
AU  - Feng J
FAU - Sun, Haosheng
AU  - Sun H
FAU - Scobie, Kimberly N
AU  - Scobie KN
FAU - Damez-Werno, Diane
AU  - Damez-Werno D
FAU - Crumiller, Marshall
AU  - Crumiller M
FAU - Ohnishi, Yoshinori N
AU  - Ohnishi YN
FAU - Ohnishi, Yoko H
AU  - Ohnishi YH
FAU - Mouzon, Ezekiell
AU  - Mouzon E
FAU - Dietz, David M
AU  - Dietz DM
FAU - Lobo, Mary Kay
AU  - Lobo MK
FAU - Neve, Rachael L
AU  - Neve RL
FAU - Russo, Scott J
AU  - Russo SJ
FAU - Han, Ming-Hu
AU  - Han MH
FAU - Nestler, Eric J
AU  - Nestler EJ
LA  - eng
GR  - R01 MH092306/MH/NIMH NIH HHS/United States
GR  - P01 DA008227/DA/NIDA NIH HHS/United States
GR  - K99 MH094405/MH/NIMH NIH HHS/United States
GR  - T32 MH087004/MH/NIMH NIH HHS/United States
GR  - R01 DA014133/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 76I7G6D29C (Morphine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Dopamine/metabolism
MH  - Dopaminergic Neurons/*drug effects/physiology
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Gene Knockout Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Morphine/*pharmacology
MH  - Morphine Dependence/genetics/*physiopathology
MH  - Nucleus Accumbens/drug effects/physiopathology
MH  - Photic Stimulation
MH  - Receptor, trkB/genetics/physiology
MH  - Ventral Tegmental Area/*drug effects/physiology
PMC - PMC3547365
MID - NIHMS432501
EDAT- 2012/10/09 06:00
MHDA- 2012/10/12 06:00
PMCR- 2013/10/05
CRDT- 2012/10/09 06:00
PHST- 2012/10/09 06:00 [entrez]
PHST- 2012/10/09 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2013/10/05 00:00 [pmc-release]
AID - 338/6103/124 [pii]
AID - 10.1126/science.1222265 [doi]
PST - ppublish
SO  - Science. 2012 Oct 5;338(6103):124-8. doi: 10.1126/science.1222265.