High trait impulsivity predicts food addiction-like behavior in the rat

Abstract

Impulsivity is a behavioral trait frequently seen not only in drug-addicted individuals but also in individuals who pathologically overeat. However, whether impulsivity predates the development of uncontrollable feeding is unknown. In this study, we hypothesized that a high impulsivity trait precedes and confers vulnerability for food addiction-like behavior. For this purpose, we trained ad libitum-fed male Wistar rats in a differential reinforcement of low rates of responding (DRL) task to select Low- and High-impulsive rats. Then, we allowed Low- and High-impulsive rats to self-administer a highly palatable diet (Palatable group) or a regular chow diet (Chow group) in 1-h daily sessions, under fixed ratio (FR) 1, FR3, FR5, and under a progressive ratio (PR) schedules of reinforcement. In addition, we tested the compulsiveness for food in Low- and High-impulsive rats by measuring the food eaten in the aversive, open compartment of a light/dark conflict test. Finally, we measured the expression of the transcription factor ΔFosB in the shell and the core of the nucleus accumbens, which is a marker for neuroadaptive changes following addictive drug exposure. The data we obtained demonstrate that impulsivity is a trait that predicts the development of food addiction-like behaviors, including: (i) excessive intake, (ii) heightened motivation for food, and (iii) compulsive-like eating, when rats are given access to highly palatable food. In addition, we show that the food addiction phenotype in high impulsive subjects is characterized by an increased expression of the transcription factor ΔFosB in the nucleus accumbens shell. These results reveal that impulsivity confers an increased propensity to develop uncontrollable overeating of palatable food.

Figure 1

Impulsivity is a phenotype distinct from both novelty-induced locomotor activity and anxiety-like behavior. (a) Left: Screening for Low- and High-responsive rats based on spontaneous locomotor reactivity to novelty. High-responsive rats show higher locomotor activity than Low-responsive rats. (a) Right: Low- and High-responsive rats do not differ in their tendency to respond prematurely in the DRL task. (b) Left: Screening for Low- and High-impulsive rats using a DRL task. High-impulsive rats are less efficient in responding compared with Low-impulsive rats. (b) Right: Low- and High-impulsive rats do not differ in novelty-induced locomotor activity. (c) Left: Screening for Low- and High-anxiety rats based on the percentage of open arm time in the elevated plus-maze. High-anxiety rats show lower percentage of open arm time than Low-anxiety rats. (c) Right: Low- and High-anxiety rats do not differ in their tendency to respond prematurely in the DRL task. (d) Low- and High-impulsive rats (screened in panel (b) left) do not differ in anxiety-like behavior. n=8/9 group. Data show M±SEM. ***p⩽0.0001 vs Low counterpart.

Figure 2

High trait impulsivity predicts the disruption of neophobia, the escalation of highly palatable food intake, the motivation for, and the compulsive-like eating of highly palatable food. (a) Screening for Low- and High-impulsive rats using a DRL task. High-impulsive rats are less efficient in responding compared with Low-impulsive rats. (b) One-hour food intake during the first day of palatable food self-administration in Low- and High-impulsive rats. Expectedly Low-impulsive/Palatable rats showed food neophobia, contrary to High-impulsive/Palatable rats who readily accepted the new diet. (c) Effects of daily, 1-h access to a highly palatable diet on food intake in Low- and High-impulsive rats. High-impulsive/Palatable rats dramatically escalated responding for the highly palatable diet, resulting in a significantly higher food intake compared with all other groups. (d) Effects of daily, one-hour access to a highly palatable diet on food intake under FR3 and FR5 schedules of reinforcement. High-impulsive/Palatable rats showed higher responding for food compared with all other groups. (e) Motivation for food, measured as the breakpoint under a progressive-ratio schedule of reinforcement. High-impulsive/Palatable rats showed higher breakpoint for food than all the other groups. (f) Compulsive-like eating behavior measured in the light/dark conflict test. High-impulsive/Palatable rats showed higher food intake compared with all other groups. n=29. Data show mean±SEM. ^@@@p⩽0.001 High-impulsive/Chow vs Low-impulsive/Chow; ^#p⩽0.05, Low-impulsive/Palatable vs Low-impulsive/Chow; *p⩽0.01, **p⩽0.001, ***p⩽0.0001 High-impulsive/Palatable vs Low-impulsive/Palatable.

Figure 3

Food addiction-like score highly correlates with escalated intake, motivation for food, and compulsive-like eating. (a–c) Excessive intake, motivation for food, and compulsive-like eating as a function of the number of positive food addiction-like criteria met. The intensity of the three food addiction-like behaviors was proportional to the number of positive criteria met by the subjects. (d–f) The food addiction-like score highly correlated with excessive intake, motivation for food, and compulsive-like eating. n=29. Data show mean±SEM. ^$p⩽0.05, ^$$p⩽0.01, ^$$$p⩽0.001 vs zero criteria group.

Figure 4

Three criteria and High-impulsive/Palatable rats show highest food addiction-like score. (a) Rats with the three criteria showed a food addiction-like score (3.72±0.47) above the SD of all rats (2.41) and higher than any other groups. (b) Food addiction-like score as function of the four experimental groups. The food addiction-like score in High-impulsive/Palatable rats was higher than in all other. (c) Percentage of the total population of Low- and High-impulsive/Chow and Palatable rats positive for zero, one, two, or three food addiction-like criteria. n=29. Data show mean±SEM. ^$$p⩽0.01, ^$$$p⩽0.001 vs zero criteria group; ^#p⩽0.05; ^###p⩽0.001 vs Low-impulsive/Chow; ***p⩽0.001 vs Low-impulsive/Palatable.

Figure 5

ΔFosB expression in the nucleus accumbens (NAcc). (a and d) ΔFosB expression in the NAcc core and shell expressed as density change (%) in relation to the Low-impulsive/Chow group. High-impulsive/Palatable animals showed a significant increase in both regions compared with the Low-impulsive/Chow group and a significant increase in the NAcc core compared with the Low-impulsive/Palatable. (b and e) Food addiction-like behavior highly correlated with ΔFosB expression in the NAcc shell but not in the NAcc core. (c and f) Representative micrographs ( × 20) of ΔFosB expression in NAcc core and shell of the different groups are shown. n=23. Data show mean±SEM. ^#p⩽0.05, ^##p⩽0.01, ^###p⩽0.001 vs Low-impulsive/Chow; *p⩽0.05 vs Low-impulsive/Palatable.