Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity

Abstract

Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/ or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or 'wanting'). We also assessed dietvs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened 'wanting' was not due to individual differences in the hedonic impact ('liking') of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal 'hotspots' that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation. INTRODUCTIONPavlovian cues associated with palatable foods (food cues), like the smell of fresh-baked brownies, carry incentive salience that makes the cues attractive, reinforcing, and able to trigger urges to eat. For example, in humans, food cues can increase ratings of desire to eat and the amount of food consumed (Fedoroff et al, 1997;Soussignan et al, 2012). Similarly, in rodents, food cues can elicit approach, reinforce operant responding (eg, conditioned reinforcement), and increase food consumption (Holland and Petrovich, 2005). However, no studies have examined cue-induced motivation in preclinical models of obesity. The recent global rise in obesity heightens the need to understand the neurobiological mechanisms governing these processes, particularly in susceptible individuals.Clinical data suggest that some people may attribute more incentive salience (ie, motivational value) to food cues than others, and consequently be more likely to overeat and become obese (see Dagher, 2009 for review). For example, food cues more robustly enhance the desire to eat (Fedoroff et al, 1997;Tetley et al, 2009) and more strongly activate the nucleus accumbens (NAc) and caudate putamen (CPu) in obese people (Rothemund et al, 2007;Stoeckel et al, 2008), even prior to t...

Obesity-Induced Structural and Neuronal Plasticity in the Lateral Orbitofrontal Cortex

“…We propose that this is due to a change in response priority due to the incentive value of the food and not a change in Pavlovian or instrumental learning, as obese rats were capable of both appetitive and aversive conditioning. Consistent with these findings, others have demonstrated that cafeteria-diet-induced obesity show increased conditioned approach behaviours likely to due to the enhanced incentive value of the food without a change in the rate of acquisition of Pavlovian learning (Robinson et al, 2015). Rats with restricted access to a cafeteria diet exhibited binge-like eating behaviour such that they consumed 2/3 of their daily caloric needs within 1 h and that they had elevated baseline feeding in the operant chambers compared to extended access rats.…”

Homeostasis Meets Motivation in the Battle to Control Food Intake

“…A central observation is that, compared with normal weight controls, overweight and obese humans show reduced striatal D2R availability Stice et al, 2008b;Kenny et al, 2013) and individuals with the Taq1A A1 allele, which is associated with reduced D2R expression, are more likely to be obese (Stice et al, 2008b). Obese and overweight individuals also show enhanced striatal activation in response to food-predictive cues (Rothemund et al, 2007;Stoeckel et al, 2008;Demos et al, 2012), but reduced striatal activation following palatable food receipt (Stice et al, 2008a, b;Babbs et al, 2013). Importantly these striatal reactivity observations, which may reflect reward prediction error signals (Kroemer and Small, 2016), are also predictive of future weight gain, indicating that striatal network activity is closely linked with the development of obesity Demos et al, 2012).…”

“…However, reduced striatal D2R expression is seen in rodents fed a junk-food diet regardless of the whether they develop obesity or not (Robinson et al, 2015), suggesting that this striatal adaptation cannot fully explain maladaptive weight gain (Kroemer and Small, 2016). A more parsimonious explanation emerging from the literature is one in which individual susceptibility interacts with the types of foods consumed to alter striatal function and promote cue-induced food-seeking behavior (Stice et al, 2008b(Stice et al, , 2009Stoeckel et al, 2008;Felsted et al, 2010;Albuquerque et al, 2015;Brown et al, 2015b;Robinson et al, 2015). This chain of events may then be further exacerbated by increased adiposity and metabolic dysfunction that characterize obesity.…”

“…In these studies, diet-induced alterations in NAc function occurred in the absence of obesity, suggesting that these changes may drive overconsumption that promotes subsequent weight gain. Diet-induced increases in NAc calcium-permeable AMPARs are particularly interesting because these receptors mediate enhanced cue-triggered drug craving (Loweth et al, 2014;Terrier et al, 2016;Wolf, 2016) and cue-induced motivation for food is enhanced in obese and obesity-susceptible rats and humans (Small, 2009;Stice et al, 2013;Brown et al, 2015b;Robinson et al, 2015).…”

“…For example, chronic overconsumption of saturated but not monounsaturated dietary lipids dampens NAc DA signaling in the absence of obesity (Hryhorczuk et al, 2016) and consumption of triglycerides acutely reduces food-seeking behavior (Cansell et al, 2014). Diet and obesity also induce changes in NAc DA receptor expression and transmission, which differ between obesitysusceptible and resistant populations (Geiger et al, 2009;Robinson et al, 2015;Valenza et al, 2015;Vollbrecht et al, 2016). These data lend support to the idea that individual susceptibility to obesity influences both neural and behavioral observations that promote weight gain (Stice et al, 2008b;Felsted et al, 2010;Albuquerque et al, 2015).…”