The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine

H Cui; M Lutter

doi:10.1111/gbb.12057

Back

The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine

Journal article

Open access

Peer reviewed

The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine

H Cui and M Lutter

Genes, brain and behavior, Vol.12(6), pp.658-665

08/2013

DOI: 10.1111/gbb.12057

PMCID: PMC3782389

PMID: 23786641

Files and links (1)

url

https://doi.org/10.1111/gbb.12057View

Published (Version of record) Open Access

Abstract

While it is known that mice lacking melanocortin 4 receptor (MC4R) expression develop hyperphagia resulting in early-onset obesity, the specific neural circuits that mediate this process remain unclear. Here, we report that selective restoration of MC4R expression within dopamine-1 receptor-expressing neurons [MC4R/dopamine 1 receptor (D1R) mice] partially blunts the severe obesity seen in MC4R-null mice by decreasing meal size, but not meal frequency, in the dark cycle. We also report that both acute cocaine-induced anorexia and the development of locomotor sensitization to repeated administration of cocaine are blunted in MC4R-null mice and normalized in MC4R/D1R mice. Neuronal retrograde tracing identifies the lateral hypothalamic area as the primary target of MC4R-expressing neurons in the nucleus accumbens. Biochemical studies in the ventral striatum show that phosphorylation of DARPP-32(Thr) (-34) and GluR1(Ser) (-845) is diminished in MC4R-null mice after chronic cocaine administration but rescued in MC4R/D1R mice. These findings highlight a physiological role of MC4R-mediated signaling within D1R neurons in the long-term regulation of energy balance and behavioral responses to cocaine.

Phosphorylation

Nucleus Accumbens - metabolism

Basal Ganglia - metabolism

Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics

Receptor, Melanocortin, Type 4 - metabolism

Anorexia - genetics

Receptors, Dopamine D1 - metabolism

Dopaminergic Neurons - metabolism

Nucleus Accumbens - cytology

Dopaminergic Neurons - drug effects

Receptors, AMPA - genetics

Receptors, AMPA - metabolism

Eating

Mice, Inbred C57BL

Receptor, Melanocortin, Type 4 - genetics

Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism

Mice, Knockout

Cocaine - pharmacology

Locomotion

Animals

Cocaine - toxicity

Anorexia - chemically induced

Mice

Nucleus Accumbens - drug effects

Receptors, Dopamine D1 - genetics

Details

Title: Subtitle: The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine
Creators: H Cui - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Huxing-Cui@uiowa.edu
M Lutter
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.12(6), pp.658-665
Publisher: England
DOI: 10.1111/gbb.12057
PMID: 23786641
PMCID: PMC3782389
ISSN: 1601-1848
eISSN: 1601-183X
Grant note: PL1 DK081182 / NIDDK NIH HHS K08 MH084058 / NIMH NIH HHS MH084058-01A1 / NIMH NIH HHS RL1 DK081185 / NIDDK NIH HHS DK081182-01 / NIDDK NIH HHS DK081185-01 / NIDDK NIH HHS
Language: English
Date published: 08/2013
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040490502771

Metrics

18 Record Views

30 Times Cited - Web of Science

See more details