PMID- 27408780
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160713
LR  - 20191218
IS  - 2212-8778 (Print)
IS  - 2212-8778 (Electronic)
IS  - 2212-8778 (Linking)
VI  - 5
IP  - 7
DP  - 2016 Jul
TI  - Melanocortin-3 receptors in the limbic system mediate feeding-related 
      motivational responses during weight loss.
PG  - 566-579
LID - S2212-8778(16)30034-5 [pii]
LID - 10.1016/j.molmet.2016.05.002 [doi]
AB  - OBJECTIVE: Appetitive responses to weight loss are mediated by a nutrient-sensing 
      neural network comprised of melanocortin neurons. The role of neural 
      melanocortin-3 receptors (MC3R) in mediating these responses is enigmatic. Mc3r 
      knockout mice exhibit a paradoxical phenotype of obesity and reduced 
      feeding-related behaviors in situations of nutrient scarcity. Here we examined 
      whether MC3Rs expressed in mesolimbic neurons regulate feeding-related 
      motivational responses. METHODS: Interactions between Mc3r genotype, cognitive 
      function and energy balance on food self-administration were assessed using 
      operant conditioning with fixed- and progressive ratio (FR1/PR1) settings. 
      Inhibition of Mc3r transcription by a loxP-flanked transcriptional blocker (TB) 
      in C57BL/6JN mice (Mc3r (TB/TB) ) was reversed in mesolimbic neurons using 
      DAT-Cre (DAT-MC3R). RESULTS: Caloric restriction (CR) caused 10-15% weight loss 
      and increased motivation to acquire food rewards during training sessions. 
      c-Fos-expression in the nucleus accumbens was increased 1 h following food 
      presentation. While exhibiting weight loss, total food self-administration, 
      enhanced motivation to self-administer food rewards in training sessions held 
      during CR and c-Fos-activation in the nucleus accumbens following re-feeding were 
      all markedly attenuated in Mc3r (TB/TB) mice. In contrast, cognitive abilities 
      were normal in Mc3r (TB/TB) mice. Total food self-administration during FR1 
      sessions was not rescued in DAT-MC3R mice, however enhanced motivational 
      responses to self-administer food rewards in PR1 conditions were restored. The 
      nutrient-partitioning phenotype observed with Mc3r-deficiency was not rescued in 
      DAT-MC3R mice. CONCLUSIONS: Mesolimbic MC3Rs mediate enhanced motivational 
      responses during CR. However, they are insufficient to restore normal caloric 
      loading when food is presented during CR and do not affect metabolic conditions 
      altering nutrient partitioning.
FAU - Mavrikaki, Maria
AU  - Mavrikaki M
AD  - Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 
      33458, USA; Department of Pharmacology & Physiology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104, USA.
FAU - Girardet, Clemence
AU  - Girardet C
AD  - Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 
      33458, USA; Department of Pharmacology & Physiology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104, USA.
FAU - Kern, Andras
AU  - Kern A
AD  - Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 
      33458, USA.
FAU - Faruzzi Brantley, Alicia
AU  - Faruzzi Brantley A
AD  - Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, 
      USA; Behavioral Core, The Scripps Research Institute, Jupiter, FL 33458, USA.
FAU - Miller, Courtney A
AU  - Miller CA
AD  - Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 
      33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, 
      FL 33458, USA.
FAU - Macarthur, Heather
AU  - Macarthur H
AD  - Department of Pharmacology & Physiology, Saint Louis University School of 
      Medicine, St. Louis, MO 63104, USA.
FAU - Marks, Daniel L
AU  - Marks DL
AD  - Pape Family Pediatric Research Institute, Oregon Health & Science University, 
      Portland, OR 97239, USA.
FAU - Butler, Andrew A
AU  - Butler AA
AD  - Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 
      33458, USA; Department of Pharmacology & Physiology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104, USA. Electronic address: 
      Butleraa@slu.edu.
LA  - eng
GR  - R01 DA034116/DA/NIDA NIH HHS/United States
GR  - R01 DK073189/DK/NIDDK NIH HHS/United States
GR  - R03 DA033499/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20160512
PL  - Germany
TA  - Mol Metab
JT  - Molecular metabolism
JID - 101605730
PMC - PMC4921936
OTO - NOTNLM
OT  - Appetite
OT  - Caloric restriction
OT  - Dopamine
OT  - Melanocortin-3 receptors
OT  - Melanocortins
OT  - Motivation
EDAT- 2016/07/14 06:00
MHDA- 2016/07/14 06:01
PMCR- 2016/05/12
CRDT- 2016/07/14 06:00
PHST- 2016/04/01 00:00 [received]
PHST- 2016/04/28 00:00 [revised]
PHST- 2016/05/04 00:00 [accepted]
PHST- 2016/07/14 06:00 [entrez]
PHST- 2016/07/14 06:00 [pubmed]
PHST- 2016/07/14 06:01 [medline]
PHST- 2016/05/12 00:00 [pmc-release]
AID - S2212-8778(16)30034-5 [pii]
AID - 10.1016/j.molmet.2016.05.002 [doi]
PST - epublish
SO  - Mol Metab. 2016 May 12;5(7):566-579. doi: 10.1016/j.molmet.2016.05.002. 
      eCollection 2016 Jul.