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 diet- vs 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 'hot-spots' 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.

Figure 1

Junk-Food Gainers show enhanced conditioned approach prior to junk-food diet exposure. (a) Average (±SEM) weekly weight gain prior to (week 1–3) and during (week 4–7) junk-food diet exposure. (b) Average conditioned approach behavior (total CS lever presses and food-cup entries during the CS period) across autoshaping sessions prior to junk-food diet exposure is greater in Junk-Food Gainers vs Junk-Food Non-Gainers. (c) Responding during the inter-trial-interval (ITI; ie, in the absence of the sucrose cue) decreased across sessions and did not differ between groups after acquisition. (d) Average (±SEM) sign-tracking (CS lever presses) and (e) goal-tracking (food-cup entries during the CS period) across autoshaping sessions conducted prior to junk-food diet exposure (main effect of group *p<0.05).

Figure 2

Willingness to obtain the sucrose cue is enhanced in Junk-Food Gainers vs Junk-Food Non-Gainers after junk-food diet exposure and tendency towards sign-tracking and goal-tracking does not ‘map on’ to susceptibility to obesity. (a) Average (±SEM) weekly weight gain (upper panel), whereas lower panels from left to right show: starting weight, weight gain during the first week of junk-food diet exposure, and plasma levels of leptin and fasted insulin after 15 weeks of junk-food diet exposure. (b) Average conditioned approach behavior (total CS lever presses and food-cup entries during the CS period) across autoshaping sessions prior to junk-food diet exposure did not differ between groups when animals were trained food-restricted. (c) Average (±SEM) sign-tracking (CS lever presses) and (d) goal-tracking (food-cup entries during the CS period) across autoshaping sessions while food-restricted. (e) Bias towards sign-tracking and goal-tracking for individual rats trained while food-restricted (triangles) or trained while ad lib fed (circles) did not differ. (f) Average number (±SEM) of active and inactive nose-poke responses during instrumental conditioned reinforcement testing. JF-Gainers and Chow-Fed rats were willing to work for a presentation of the sucrose cue, whereas JF-Non-Gainers were not (active vs inactive; *p<0.05).

Figure 3

Cross-sensitization to amphetamine. Average number of beam breaks (±SEM) per 25 min after injection of saline (1 ml/kg) or 4 doses of d-amphetamine (0.32, 1, 3.2, 5.6 mg/kg, i.p.). Regardless of weight gain, rats fed a junk-food diet showed a sensitized locomotor response to amphetamine compared with Chow-Fed rats (main effect of group *p<0.05; see also Supplementary Figure 2).

Figure 4

Junk-food diet exposure decreases D2R mRNA expression in rostral NAc, regardless of weight gain. (a) Average D2R mRNA expression (±SEM) in the rostral NAc core and shell is decreased in all rats fed a junk-food diet, regardless of weight gain, compared with Chow-Fed rats (Junk-Food vs Chow-Fed *p<0.05). (b) Average D1R mRNA (±SEM) in CPu and NAc was significantly greater in JF-Non-Gainers vs JF-Gainers and vs Chow-Fed rats (JF-Non-Gainer vs JF-Gainer main effect of group ^#p<0.05, Chow-Fed vs JF-Non-Gainer main effect of group ^$p<0.05). (c) Average (±SEM) TH D2R, and DAT mRNA expression in the VTA. TH mRNA expression was significantly decreased in JF-G vs JF-Ns (*p<0.05).

Figure 5

MuR mRNA expression is lower in feeding ‘hot-spots’ of Junk-Food Gainers vs Junk-Food Non-Gainers and hedonic responses to oral sucrose administration. (a) Average MuR mRNA expression (±SEM) in the rostral shell ‘liking’ hot-spot and caudal shell, (b) in the dorsal-medial CPu ‘wanting’ hot-spot, and (d) the anterior central CPu are significantly lower in JF-Gainers than in JF-Non-Gainers (*p<0.05). Average MuR mRNA expression (±SEM) in dorsal-lateral CPu (c), ventral-lateral CPu (e), ventral-medial CPu (f), and NAc Core (g) did not differ between groups. (h) Average positive hedonic response (±SEM) to increasing concentrations of sucrose prior to (Pre-JF) and after 1 month of junk-food diet exposure (Post-JF). Prior to junk-food diet exposure, hedonic responses to sucrose did not differ in rats subsequently identified as Junk-Food Gainers and Junk-Food Non-Gainers, and increasing concentrations of sucrose elicited increasingly stronger positive hedonic responses (main effect of concentration *p<0.05). After junk-food diet exposure, all concentrations of sucrose elicited similar levels of positive hedonic responses, with Junk-Food Non-Gainers generally showing stronger positive response than Junk-Food Gainers (see also Supplementary Figure 4).