Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity

• Published in: Behavioural brain research Vol. 210; no. 2; pp. 155 - 163
• Main Authors: Mathes, Wendy Foulds, Nehrenberg, Derrick L., Gordon, Ryan, Hua, Kunjie, Garland, Theodore, Pomp, Daniel
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 11.07.2010; Elsevier
• Subjects: Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Analysis of Variance; Animals; Behavioral psychophysiology; Biogenic Monoamines - metabolism; Biological and medical sciences; Body weight; Body Weight - physiology; Breeding; Chromatography, High Pressure Liquid - methods; Corpus Striatum - metabolism; Dopamine - genetics; Dopamine - metabolism; Dorsal striatum; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - physiology; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred Strains; Microarray; Microfilament Proteins - metabolism; Monoamines; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nuclear Proteins - metabolism; Nucleus accumbens; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - mortality; Physical activity; Physical Conditioning, Animal - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Selection, Genetic - physiology; Signal Transduction - genetics; Species Specificity; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; Nucleus accumbens; Physical activity; Body weight; Microarray; Gene expression; Monoamines; Dorsal striatum; Physical exercise; Obesity; Dopamine; Rodentia; Central nervous system; Nutrition disorder; Monoamine; Basal ganglion; Corpus striatum; Catecholamine; Encephalon; Vertebrata; Mammalia; Mouse; Animal; Neurotransmitter; Nutritional status
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.02.016

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.