Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain

Abstract

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 the present study we examined diet effects on expression and function of the dopamine transporter (DAT) in caudate-putamen (CPu), nucleus accumbens (NAc), and midbrain regions. DA uptake by CPu, NAc or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [ ³H]DA uptake and was found to correlate with DA transporter (DAT) surface expression, assessed by maximal [ ³H]CFT binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CPu with a corresponding decrease in surface expression but had no effects in the NAc and midbrain. Diet treatments also affected sensitivity to insulin-induced enhancement of DA uptake, with FR producing an increase in CPu and NAc, likely mediated by an observed increase in insulin receptor (InsR) expression, and OB producing a decrease in NAc. The increased expression of InsR in NAc of FR rats was accompanied by increased DA D ₂ receptor (D ₂R) expression, and the decreased DAT expression and function in CPu of OB rats was accompanied by decreased D ₂R 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.

Graphical Abstract

Food restricted (FR) or obesogenic (OB) diets are known to oppositely alter behavioral responses to psychostimulants that target the dopamine transporter (DAT). Here we report the relationship between DAT-mediated DA uptake at baseline (red) and with acute insulin stimulation (blue) in synaptosomes isolated from nucleus accumbens (NAc) and caudate-putamen (CPu) of FR and OB rats compared to ad libitum (AL) fed rats. Regional differences in total expression of DAT, insulin receptor (InsR) and dopamine D ₂ receptor (D ₂R) are further observed thereby providing some insights into psychostimulant sensitivity with diet.