Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward

Melissa A. Stouffer, Catherine A. Woods, Jyoti C. Patel, Christian R. Lee, Paul Witkovsky, Li Bao, Robert P. Machold, Kymry T. Jones, Soledad Cabeza de Vaca, Maarten E. A. Reith, Kenneth D. Carr and Margaret E. Rice ()
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Melissa A. Stouffer: New York University School of Medicine
Catherine A. Woods: Center for Neural Science, New York University
Jyoti C. Patel: New York University School of Medicine
Christian R. Lee: New York University School of Medicine
Paul Witkovsky: New York University School of Medicine
Li Bao: New York University School of Medicine
Robert P. Machold: Smilow Neuroscience Program, New York University School of Medicine
Kymry T. Jones: New York University School of Medicine
Soledad Cabeza de Vaca: New York University School of Medicine
Maarten E. A. Reith: New York University School of Medicine
Kenneth D. Carr: New York University School of Medicine
Margaret E. Rice: New York University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate–putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices.

Date: 2015
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DOI: 10.1038/ncomms9543

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