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Interactions between insulin and diet on striatal dopamine uptake kinetics in rodent brain slices
Author(s) -
Patel Jyoti C.,
Stouffer Melissa A.,
Mancini Maria,
Nicholson Charles,
Carr Kenneth D.,
Rice Margaret E.
Publication year - 2019
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13958
Subject(s) - medicine , endocrinology , dopamine , insulin , nucleus accumbens , insulin receptor , dopamine transporter , dopamine receptor d2 , cholinergic , chemistry , biology , insulin resistance , dopaminergic
Diet influences dopamine transmission in motor‐ and reward‐related basal ganglia circuitry. In part, this reflects diet‐dependent regulation of circulating and brain insulin levels. Activation of striatal insulin receptors amplifies axonal dopamine release in brain slices, and regulates food preference in vivo . The effect of insulin on dopamine release is indirect, and requires striatal cholinergic interneurons that express insulin receptors. However, insulin also acts directly on dopamine axons to increase dopamine uptake by promoting dopamine transporter ( DAT ) surface expression, counteracting enhanced dopamine release. Here, we determined the functional consequences of acute insulin exposure and chronic diet‐induced changes in insulin on DAT activity after evoked dopamine release in striatal slices from adult ad‐libitum fed ( AL ) rats and mice, and food‐restricted ( FR ) or high‐fat/high‐sugar obesogenic ( OB ) diet rats. Uptake kinetics were assessed by fitting evoked dopamine transients to the Michaelis‐Menten equation and extracting C peak and V max . Insulin (30 n m ) increased both parameters in the caudate putamen and nucleus accumbens core of AL rats in an insulin receptor‐ and PI 3‐kinase‐dependent manner. A pure effect of insulin on uptake was unmasked using mice lacking striatal acetylcholine, in which increased V max caused a decrease in C peak . Diet also influenced V max , which was lower in FR vs. AL . The effects of insulin on C peak and V max were amplified by FR but blunted by OB , consistent with opposite consequences of these diets on insulin levels and insulin receptor sensitivity. Overall, these data reveal acute and chronic effects of insulin and diet on dopamine release and uptake that will influence brain reward pathways.