PMID- 18657800
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20211020
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 64
IP  - 11
DP  - 2008 Dec 1
TI  - Delta FosB-mediated alterations in dopamine signaling are normalized by a 
      palatable high-fat diet.
PG  - 941-50
LID - 10.1016/j.biopsych.2008.06.007 [doi]
AB  - BACKGROUND: Sensitivity to reward has been implicated as a predisposing factor 
      for behaviors related to drug abuse as well as overeating. However, the 
      underlying mechanisms contributing to reward sensitivity are unknown. We 
      hypothesized that a dysregulation in dopamine signaling might be an underlying 
      cause of heightened reward sensitivity whereby rewarding stimuli could act to 
      normalize the system. METHODS: We used a genetic mouse model of increased reward 
      sensitivity, the Delta FosB-overexpressing mouse, to examine reward pathway 
      changes in response to a palatable high-fat diet. Markers of reward signaling in 
      these mice were examined both basally and following 6 weeks of palatable diet 
      exposure. Mice were examined in a behavioral test following high-fat diet 
      withdrawal to assess the vulnerability of this model to removal of rewarding 
      stimuli. RESULTS: Our results demonstrate altered reward pathway activation along 
      the nucleus accumbens-hypothalamic-ventral tegmental area circuitry resulting 
      from overexpression of Delta FosB in the nucleus accumbens and striatal regions. 
      Levels of phosphorylated cyclic adenosine monophosphate (cAMP) response element 
      binding protein (pCREB), brain-derived neurotrophic factor (BDNF), and dopamine 
      and cyclic adenosine monophosphate regulated phosphoprotein with a molecular mass 
      of 32 kDa (DARPP-32) in the nucleus accumbens were reduced in Delta FosB mice, 
      suggestive of reduced dopamine signaling. Six weeks of high-fat diet exposure 
      completely ameliorated these differences, revealing the potent rewarding capacity 
      of a palatable diet. Delta FosB mice also showed a significant increase in 
      locomotor activity and anxiety-related responses 24 hours following high-fat 
      withdrawal. CONCLUSIONS: These results establish an underlying sensitivity to 
      changes in reward related to dysregulation of Delta FosB and dopamine signaling 
      that can be normalized with palatable diets and may be a predisposing phenotype 
      in some forms of obesity.
FAU - Teegarden, Sarah L
AU  - Teegarden SL
AD  - Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 
      19104-6046, USA.
FAU - Nestler, Eric J
AU  - Nestler EJ
FAU - Bale, Tracy L
AU  - Bale TL
LA  - eng
GR  - R01 DA07359/DA/NIDA NIH HHS/United States
GR  - R01 DA007359/DA/NIDA NIH HHS/United States
GR  - P50 MH066172/MH/NIMH NIH HHS/United States
GR  - P30 DK019525-31/DK/NIDDK NIH HHS/United States
GR  - R37 DA007359/DA/NIDA NIH HHS/United States
GR  - R01 MH051399-15/MH/NIMH NIH HHS/United States
GR  - P50 MH66172/MH/NIMH NIH HHS/United States
GR  - R37 DA007359-15/DA/NIDA NIH HHS/United States
GR  - R01 MH51399/MH/NIMH NIH HHS/United States
GR  - DK019525/DK/NIDDK NIH HHS/United States
GR  - R01 MH051399/MH/NIMH NIH HHS/United States
GR  - P30 DK019525/DK/NIDDK NIH HHS/United States
GR  - R01 DA007359-18/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080726
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Dietary Fats)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Fosb protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (Crebbp protein, mouse)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Body Weight/drug effects/genetics
MH  - CREB-Binding Protein/metabolism
MH  - Cyclin-Dependent Kinase 5/metabolism
MH  - *Dietary Fats/pharmacology
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Eating/drug effects/genetics
MH  - Exploratory Behavior/drug effects/physiology
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neuropeptides/metabolism
MH  - Nucleus Accumbens/metabolism
MH  - Orexins
MH  - Proto-Oncogene Proteins c-fos/genetics/*metabolism
MH  - *Reward
MH  - Signal Transduction/genetics/*physiology
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Ventral Tegmental Area/drug effects/metabolism
PMC - PMC2582592
MID - NIHMS72016
EDAT- 2008/07/29 09:00
MHDA- 2009/04/09 09:00
PMCR- 2009/12/01
CRDT- 2008/07/29 09:00
PHST- 2008/01/15 00:00 [received]
PHST- 2008/06/06 00:00 [revised]
PHST- 2008/06/07 00:00 [accepted]
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - S0006-3223(08)00704-X [pii]
AID - 10.1016/j.biopsych.2008.06.007 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2008 Dec 1;64(11):941-50. doi: 10.1016/j.biopsych.2008.06.007. 
      Epub 2008 Jul 26.