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Effects of diet and insulin on dopamine transporter activity and expression in rat caudate‐putamen, nucleus accumbens, and midbrain
Author(s) -
Jones Kymry T.,
Woods Catherine,
Zhen Juan,
Antonio Tamara,
Carr Kenneth D.,
Reith Maarten E. A.
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13930
Subject(s) - nucleus accumbens , medicine , endocrinology , dopamine , dopamine transporter , chemistry , caudate nucleus , forebrain , midbrain , putamen , insulin , biology , central nervous system , dopaminergic
Food restriction ( FR ) and obesogenic ( OB ) diets are known to alter brain dopamine transmission and exert opposite modulatory effects on behavioral responsiveness to psychostimulant drugs of abuse. Mechanisms underlying these diet effects are not fully understood. In this study, we examined diet effects on expression and function of the dopamine transporter ( DAT ) in caudate‐putamen ( CP u), nucleus accumbens ( NA c), and midbrain regions. Dopamine ( DA ) uptake by CP u, NA c or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [ 3 H] DA uptake and was found to correlate with DAT surface expression, assessed by maximal [ 3 H](–)‐2‐β‐carbomethoxy‐3‐β‐(4‐fluorophenyl)tropane binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CP u with a corresponding decrease in surface expression but had no effects in the NA c and midbrain. Diet treatments also affected sensitivity to insulin‐induced enhancement of DA uptake, with FR producing an increase in CP u and NA c, likely mediated by an observed increase in insulin receptor expression, and OB producing a decrease in NA c. The increased expression of insulin receptor in NA c of FR rats was accompanied by increased DA D 2 receptor expression, and the decreased DAT expression and function in CP u of OB rats was accompanied by decreased DA D 2 receptor expression. These results are discussed as partial mechanistic underpinnings of diet‐induced adaptations that contribute to altered behavioral sensitivity to psychostimulants that target the DAT .