TY - JOUR
T1 - Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity
AU - Mathes, Wendy Foulds
AU - Nehrenberg, Derrick L.
AU - Gordon, Ryan
AU - Hua, Kunjie
AU - Garland, Theodore
AU - Pomp, Daniel
N1 - Funding Information:
This research was supported by NIDDK grant DK076050 (DP) and a pilot award from NIH Roadmap Grant P20RR020649 (“An Interdisciplinary Strategy for Obesity”). WFM was supported by an NIMH training grant T32MH076694 . Phenotypes were collected using the Animal Metabolism Phenotyping core facility within UNC's Clinical Nutrition Research Center (funded by NIDDK grant DK056350).
PY - 2010/7
Y1 - 2010/7
N2 - Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The results suggest that similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise.
AB - Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The results suggest that similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise.
KW - Body weight
KW - Dorsal striatum
KW - Gene expression
KW - Microarray
KW - Monoamines
KW - Nucleus accumbens
KW - Physical activity
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U2 - 10.1016/j.bbr.2010.02.016
DO - 10.1016/j.bbr.2010.02.016
M3 - Article
C2 - 20156488
AN - SCOPUS:77952323186
SN - 0166-4328
VL - 210
SP - 155
EP - 163
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -