Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.
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.
Department of Neuroscience and Physiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.|Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Melissa A
MA
Stouffer
Center for Neural Science, New York University, 4 Washington Place, New York, New York 10003, USA.
Catherine A
CA
Woods
Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Jyoti C
JC
Patel
Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Christian R
CR
Lee
Department of Ophthalmology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Paul
P
Witkovsky
Department of Neuroscience and Physiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.|Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Li
L
Bao
Smilow Neuroscience Program, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Robert P
RP
Machold
Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Kymry T
KT
Jones
Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Soledad Cabeza
SC
de Vaca
Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Maarten E A
ME
Reith
Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Kenneth D
KD
Carr
Department of Neuroscience and Physiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.|Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Margaret E
ME
Rice
D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005518:Food Preferences; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction
D007328:Insulin; D011972:Receptor, Insulin; D004298:Dopamine