Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity

Mathes, Wendy Foulds; Nehrenberg, Derrick L.; Gordon, Ryan R.; Hua, Kunjie; Garland, Theodore; Pomp, Daniel

doi:10.1016/j.bbr.2010.02.016

Cited by 89 publications

(96 citation statements)

References 55 publications

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“…Previous behavioral work (Belke and Garland 2007) suggests that HR lines have alterations in aspects of their reward system. Moreover, a general alteration of function in dopaminergic D1 receptor-mediated signaling exists in HR lines Rhodes and Garland, 2003), and recent work in one of the HR lines demonstrated elevated dopamine concentrations in both the nigrostriatal and the mesocorticolimbic pathways (Mathes et al, 2010). Both the SN and VTA contain high densities of dopaminergic neurons, and a modification in either one could be related to the functional changes already observed in the HR mice.…”

Section: Discussionmentioning

confidence: 94%

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

Kolb

Rezende

Holness

et al. 2013

Journal of Experimental Biology

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SUMMARYIncreased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P<0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.Key words: activity, allometry, cerebellum, dopamine, exercise behavior, locomotion, motor control. convergences within primates, spatio-sensory convergences within insectivores). Similar evidence for mosaic evolution in the avian brain has also been found and correlated to functional differences in the enlarged brain regions (Iwaniuk et al., 2006). Cellular changes have also been observed with increased brain size. As brain volume increases, axon diameters and the fraction of myelinated axons increase, thereby reducing the delay in neural signaling between more distant regions (Wang et al., 2008). Moreover, different cellular scaling rules apply across different mammalian orders (Herculano-Houzel, 2010). For example, in rodents, neuronal cell size increases with brain size, such that neuronal density is lower in larger-brained species (albeit with a greater absolute number of neurons) (Herculano-Houzel et al., 2006). Conversely, in primates, neuronal cell size is constant and neuron density is constant, such that total neuron number is much greater with increasing brain size (Herculano-Houzel et al., 2007). Therefore, an increase in the size of a brain region could be the product of a variety of cellular changes (e.g. neuron number, neuron density, glial density, gray-to-white matte...

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Section: Discussionmentioning

confidence: 94%

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

Kolb

Rezende

Holness

et al. 2013

Journal of Experimental Biology

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“…Studies to establish the neurohumoral circuits involved have already begun to reveal key pathways. [24][25][26] Intervention studiesFhumans…”

Section: Intervention Studiesfanimalsmentioning

confidence: 99%

Can we modulate physical activity in children?

Wilkin

2011

Int J Obes

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Intuition tells us that physical activity is central to weight reduction in obese children. Evidence, on the other hand, suggests that increases in physical activity are difficult to achieve in the short term, and may not be possible in the long term. One explanation could be an 'activitystat', a feedback loop in the child's brain that controls physical activity according to a set point. This brief article, which argues that it may not be possible to modulate the activity of children, reviews the principles of feedback control as they apply to physical activity, discusses evidence for its central control, and demonstrates how a physical activity control loop might operate to defend the set point. Studies restricted to objective measurement suggest that the physical activity of children varies in a systematic, rather than random manner. It varies little from environment to environment, from year to year or from place to place. Where children undertake more activity at one time of day, they appear to compensate at another. Systematic variation of this kind implies control, and the control of physical activity appears to lie with the child, not with his environment. Perturbation (temporary change in response to disturbance) during short-term physical activity interventions may be mistaken for modulation (permanent change in set point), a fundamentally different response. Perturbation lasts no longer than the disturbance that causes it, and there is little evidence that interventions raise activity long term, if at all.

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“…The ventral tegmental area shows stronger phasic dopamine spikes after voluntary wheel running in rats (Wang and Tsien, 2011), suggesting that neurons in the ventral tegmental area code motivational signals which trigger, sustain, or end movement. Animals that are bred for increased wheel-running have higher dopamine concentrations in the ventral striatum as measured by chromatography (Mathes et al, 2010). This makes physical exercise therapy very promising from a neurobiological point of view.…”

Section: Outlook: Possible New Therapies For Comorbid Obesitymentioning

confidence: 99%

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

Grimm

Kaiser

Plichta

et al. 2017

Neuroscience & Biobehavioral Reviews

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a b s t r a c tObesity and weight gain are severe complications of mental illness, especially schizophrenia. They result from changes in lifestyle and nutrition, side effects of medication and other, less well-understood factors. Recent studies suggest that obesity and weight gain are linked to psychopathology. Specifically, severe psychopathology is associated with greater weight dysregulation, typically weight gain. However, our knowledge about the neuroscientific basis of weight gain in schizophrenia is currently limited. We propose that altered reward anticipation, which in turn is related to striatal dopaminergic dysregulation, may explain why obesity is more prevalent in individuals with mental illness. We review evidence that reward anticipation and weight change are linked by a core deficit in dopaminergic striatal circuits. Several lines of evidence, running from animal studies to preclinical and clinical studies, suggest that striatal dopaminergic neurotransmission is a major hub for the regulation of eating behavior and that dopamine links eating behavior to other motivated behavior. From this perspective, the present review outlines a unifying perspective on dopaminergic reward anticipation as a theoretical frame to link weight gain, medication effects and psychopathology. We derive important but open empirical questions and present perspectives for new therapeutic concepts.

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Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity

Cited by 89 publications

References 55 publications

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

Can we modulate physical activity in children?

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

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