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 D2 receptor (D2R) expression, and the decreased DAT expression and function in CPu of OB rats was accompanied by decreased D2R 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.

Food restriction induces synaptic incorporation of calcium‐permeable AMPA receptors in nucleus accumbens

“…At the same time, the enhanced, but Naspm-insensitive, behavioral response to quinpirole in FR rats indicates that there is likely more than one neuroadaptation contributing to the net effect of FR on DA transmission and behavior. The recently demonstrated increase in D-2 receptor protein expression in NAc synaptoneurosomes of FR rats points to a potential mechanistic basis of the enhanced response to quinpirole (Jones et al, 2016).…”

Lost in Translation? On the Need for Convergence in Animal and Human Studies on the Role of Dopamine in Diet-Induced Obesity

“…Rodent models allow for the investigation of more causal links between obesity and dopamine transmission and have begun to disentangle the effects of an obesogenic diet from adiposity. Short-term and chronic high fat diets (HFDs) as well as diet-induced obesity were shown to reduce D2R-mRNA and protein expression levels ( [96][97][98][99], but see [100]) ( Table 2). An elegant study suggests that diet-induced obesity may be the cause rather than the result of reduced D2R availability [18••].…”

“…One study showed reduced D1R signalling when a diet high in saturated, but not monounsaturated fats (palm oil vs. olive oil), was administered [101]. Finally, diet-related changes in dopamine synthesis [108], release [59,102,105] and uptake (DAT) [98,99] have been observed.…”

Interactions between insulin and diet on striatal dopamine uptake kinetics in rodent brain slices

“…In addition to enhancing striatal DA release, insulin also increases dopamine transporter (DAT) trafficking to the plasma membrane via a PI3‐kinase (PI3K) and Akt signaling pathway, thereby increasing overall DAT activity and DA uptake (Carvelli et al ., ; Garcia et al ., ; Schoffelmeer et al ., ; Mebel et al ., ; Jones et al ., ). However, little is known about how opposite changes in circulating plasma insulin levels with FR vs. OB diets in vivo influence striatal DAT activity in intact, ex vivo striatal slices and DAT responsiveness to acute insulin exposure.…”