Long-term, calorie-restricted intake of a high-fat diet in rats reduces impulse control and ventral striatal D2 receptor signaling: two markers of addiction vulnerability (2015)

Eur J Neurosci. 2015 Nov 3. doi: 10.1111/ejn.13117.

Adams WK1,2, Sussman JL1, Kaur S1, D’souza AM3, Kieffer TJ3, Winstanley CA1,2.


High impulsivity, mediated through ventral striatal dopamine signaling, represents an established risk factor for substance abuse and may likewise confer vulnerability to pathological overeating. Mechanistically, the assumption is that trait impulsivity facilitates the initiation of maladaptive eating styles or choices. However, whether consumption of appetitive macronutrients themselves causes deficits in impulse control and striatal signaling, thereby contributing to cognitive changes permissive of overeating behavior, has yet to be considered.

We examined the effects of chronic maintenance on restricted equicaloric, yet high-fat or high-sugar, diets (48 kcal/day; 60 kcal% fat or sucrose) on rats’ performance in the 5-choice serial reaction time task (5CSRTT) indexing impulsivity and attention. Markers of dopamine signaling in the dorsal and ventral striatum, and plasma insulin and leptin levels, were also assessed. Rats maintained on the high-fat diet (HFD) were more impulsive, while the high-sugar diet (HSD) did not alter task performance. Importantly, body weight and hormone levels were similar between groups when behavioral changes were observed. Maintenance on HFD, but not HSD, reduced levels of dopamine D2 receptor (D2 R), cAMP response element-binding protein (CREB) and phospho-CREB (Ser133) proteins in the ventral, but not dorsal, striatum. D2 R expression in the ventral striatum also negatively correlated with impulsive responding independent of diet.

These data indicate that chronic exposure to even limited amounts of high-fat foods may weaken impulse control and alter neural signaling in a manner associated with vulnerability to addictions-findings that have serious implications for the propagation of uncontrolled eating behavior in obesity and binge-eating disorder.