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Does activation of midbrain dopamine neurons promote or reduce feeding?

International Journal of Obesity volume 41, pages 1131–1140 (2017)Cite this article

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Abstract

Background:

Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake.

Methods:

Here, we used designer receptors exclusively activated by designer drugs (DREADD) technology to determine the effects of enhancing DA neuronal activity on feeding behaviour. We chemogenetically activated selective midbrain DA neuronal subpopulations and assessed the effects on feeding microstructure in rats.

Results:

Treatment with the psychostimulant drug amphetamine or the selective DA reuptake inhibitor GBR 12909 significantly suppressed food intake. Selective chemogenetic activation of DA neurons in the ventral tegmental area (VTA) was found to reduce meal size, but had less impact on total food intake. Targeting distinct VTA neuronal pathways revealed that specific activation of the mesolimbic pathway towards nucleus accumbens (NAc) resulted in smaller and shorter meals. In addition, the meal frequency was increased, rendering total food intake unaffected. The disrupted feeding patterns following activation of VTA DA neurons or VTA to NAc projection neurons were accompanied by locomotor hyperactivity. Activation of VTA neurons projecting towards prefrontal cortex or amygdala, or of DA neurons in the substantia nigra, did not affect feeding behaviour.

Conclusions:

Chemogenetic activation of VTA DA neurons or VTA to NAc pathway disrupts feeding patterns. Increased activity of mesolimbic DA neurons appears to both promote and reduce food intake, by facilitating both the initiation and cessation of feeding behaviour.

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Acknowledgements

This work was funded by NeuroBasic, Full4Health (FP7-KBBE-2010-4-266408), NeuroFast (FP7/2007–2013), Nudge-IT (FP7-KBBE.2013.2.2-01), and Netherlands Organisation for Scientific Research (NWO/ALW) Veni grant. We kindly thank Bryan Roth (University of North Carolina, Chapel Hill NC, USA) and the NIMH Chemical Synthesis and Drug Supply Program for supply of CNO. We would also like to thank Ellen C Wijbrans, Anouk HA Verboven, and Jodie HK Man for assistance during experimental procedures.

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Authors and Affiliations

  1. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    L Boekhoudt, T J M Roelofs, J W de Jong, A E de Leeuw, M C M Luijendijk, I G Wolterink-Donselaar, G van der Plasse & R A H Adan

  2. Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands

    T J M Roelofs

  3. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA

    J W de Jong

  4. Department of Biomedical Engineering and Physics, Amsterdam Medical Center, Amsterdam, The Netherlands

    A E de Leeuw

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  1. L Boekhoudt
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Correspondence to R A H Adan.

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Boekhoudt, L., Roelofs, T., de Jong, J. et al. Does activation of midbrain dopamine neurons promote or reduce feeding?. Int J Obes 41, 1131–1140 (2017). https://doi.org/10.1038/ijo.2017.74

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