ArticleMolecular metabolism2015
Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Voluntary Physical Activity Modulates Brain ΔFOSB and Alters Coactivation Networks in Male and Female Mice.eNeuro · 2026Article
- Brain-wide induction of ΔFOSB and altered co-activation networks in a rat model for exercise training.Translational psychiatry · 2026Article
- Expert consensus statement for basic research of animal exercise intervention studies in chronic disease prevention and treatment: A joint position paper of the Exercise Science branch of the Biophysical Society of China and the Metabolism and Genetics branch of the Genetics Society of China.Journal of sport and health science · 2025Article
- Voluntary Running and Estrous Cycle Modulate ΔFOSB in the Suprachiasmatic Nucleus of the Wistar Rat.Journal of circadian rhythms · 2025Article
- Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats.Frontiers in endocrinology · 2023Article
- Impact of high-access exercise prior to and during early adolescence on later vulnerability to opioid use and relapse in male rats.Translational psychiatry · 2022Article
- Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors.International journal of environmental research and public health · 2022Article
- Energy Status Differentially Modifies Feeding Behavior and POMCFrontiers in endocrinology · 2021Article
- Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations.International journal of obesity (2005) · 2021 · on this mapArticle
- Aerobic Exercise and Metabolic Syndrome: The Role of Sympathetic Activity and the Redox System.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Mechanisms underlying the efficacy of exercise as an intervention for cocaine relapse: a focus on mGlu5 in the dorsal medial prefrontal cortex.Psychopharmacology · 2019Article
- Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ΔFosB.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review.Frontiers in physiology · 2018Review
- Exercise as a Prevention for Substance Use Disorder: A Review of Sex Differences and Neurobiological Mechanisms.Current addiction reports · 2017Article
- Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction.Canadian journal of physiology and pharmacology · 2017Article
- Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor.PloS one · 2017Article
- Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveMelanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome.
methodsElectrically evoked dopamine release was measured in slice preparations from sedentary wild-type and MC4R-deficient Mc4r (K314X) (HOM) rats. VWR was assessed in wild-type and HOM rats, and in MC4R-deficient loxTB (Mc4r) mice, wild-type mice body weight-matched to loxTB (Mc4r) mice, and wild-type mice with intracerebroventricular administration of the MC4R antagonist SHU9119. Mesolimbic dopamine system function (gene/protein expression) and metabolic parameters were examined in wheel-running and sedentary wild-type and HOM rats.
resultsSedentary obese HOM rats had increased electrically evoked dopamine release in several ventral tegmental area (VTA) projection sites compared to wild-type controls. MC4R loss-of-function decreased VWR, and this was partially independent of body weight. HOM wheel-runners had attenuated markers of intracellular D1-type dopamine receptor signaling despite increased dopamine flux in the VTA. VWR increased and decreased ΔFosB levels in the nucleus accumbens (NAc) of wild-type and HOM runners, respectively. VWR improved metabolic parameters in wild-type wheel-runners. Finally, moderate voluntary exercise corrected many aspects of the metabolic syndrome in HOM runners.
conclusionsCentral dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training.
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