Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors

Abstract

The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28 days of intermittent access to sucrose exhibited a deficit in the ability to block learning about a stimulus when it is paired in compound with food and another stimulus that has already been established as predictive of the food outcome. This deficit was characterized by an approach to a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. Administering the D2 agonist quinpirole during learning restored blocking in animals with a prior history of sucrose exposure. Further, repeated central infusions of ghrelin produced a deficit in blocking in the same manner as sucrose exposure. We argue that changes in dopaminergic systems resulting from sucrose exposure are mediated by a disruption of ghrelin signaling as rodents come to anticipate delivery of the highly palatable sucrose outside of normal feeding schedules. This suggestion is supported by our finding that both sucrose and ghrelin treatments resulted in increases in amphetamine-induced locomotor responding. Thus, for the first time, we have provided evidence of a potential link between alterations in D2 receptors caused by the intake of hedonic foods and aberrant learning about cue-food relationships capable of promoting inappropriate feeding habits. In addition, we have found preliminary evidence to suggest that this is mediated by changes in ghrelin signaling, a finding that should stimulate further research into modulation of ghrelin activity to treat obesity.

Adolescent Maturational Transitions in the Prefrontal Cortex and Dopamine Signaling as a Risk Factor for the Development of Obesity and High Fat/High Sugar Diet Induced Cognitive Deficits

“…In particular, intraventricular infusion of the D2R agonist quinpirole restored PFC-mediated cognitive control of learning about food cues in adult rats with a history of sucrose binging. This provides evidence of diet-induced alterations to D2R signaling mechanisms in the PFC, potentially due to a down-regulation of D2R (Sharpe et al, 2016 ).…”

“…Furthermore, the ability to reduce, or block, learning about a stimulus when it is paired in compound with another stimulus already associated with an outcome depends on the PFC (Fletcher et al, 2001 ) and midbrain dopamine signaling (Waelti et al, 2001 ). An appetitive blocking task was conducted in adult rats that had consumed sucrose in a binge-like manner for 28 days (Sharpe et al, 2016 ), the sucrose exposed animals, but not controls, approached a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. It appeared that disruption of PFC dopaminergic signaling following consumption of sucrose supplemented diets contributed to the behavioral alterations observed.…”

New Insights in Anorexia Nervosa

“…The inability of AN-R patients to respond to elevated ghrelin levels could be due to: a reduced ability to be transported to central targets within the hypothalamus (Schaeffer et al, 2013 ); a reduced GHS-R sensitivity or function; a dysregulation of hypothalamic NPY/AgRP and POMC neurons, direct or indirect targets of ghrelin effects, exerting opposing actions on food intake (Denis et al, 2014 ); an alteration in the ghrelin signaling on dopaminergic neurons, in the ventral tegmental area (VTA) (Abizaid et al, 2006 ), a structure involved in the reward/locomotion behavior, and hypothalamus to modulate appetite, respectively (Jiang et al, 2006 ; Kern et al, 2012 ; Sharpe et al, 2016 ).…”

Dopamine D2 −141C Ins/Del and Taq1A polymorphisms, body mass index, and prediction error brain response

“…This study adds evidence to the long hypothesized genetic underpinnings, specifically DA-D2R alleles, driving PE response 9 . The DA-D2R adapts to food intake and can be modified by the type of diet and weight gain 16 , 32 . This has important implications not only for conditions such as obesity and eating disorders, but also for depression and schizophrenia, conditions also often associated with high or low weight 16 , 33 .…”