Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference

Abstract

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration.

Objective: To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration.

Methods: To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period.

Results: Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered.

Discussion: Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference.

Keywords: activity-based anorexia; animal model; anorexia nervosa; brief access taste test; novel object recognition.

Figure 1

Body weight. (A) Mean ± SE body weights and (B) mean ± SE food intake for sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups. * indicates a significant difference between SED and RW vs. ABA and BWM groups p≤0.05. # indicates a significant difference between SED and BWM vs. RW and ABA groups p≤0.05. $ indicates a significant difference among SED, RW, ABA and BWM groups p≤0.05.

Figure 2

Anxiety and cognition test (A) time spent on the closed arms, platform and open arms during the elevated plus maze test, (B) time spent in the outer and inner zones during the open field test, (C) percentage time spent exploring the novel and the familiar objects during the recollection trial of the novel object recognition test, and (D) latency to enter the escape hole during the Barnes Maze test by sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups. * indicates a significant difference between time spent with the familiar and the novel object p≤0.05. Data are presented as mean ± SE.

Figure 3

Brief access taste test – Sucrose. (A) Licks across a sucrose concentration series, and (B) Number of trials initiated across the sucrose sessions for sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups. Data are presented as mean ± SE. (C) c-parameter value distribution derived from sucrose sessions for individual rats (open circles), the group means (solid lines) and SE (dashed lines) for sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups.

Figure 4

Brief access taste test – Quinine. (A) Licks across a quinine concentration series, and (B) Number of trials initiated across the quinine sessions for sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups. Data are presented as mean ± SE.

Figure 5

Diet preference test. (A) Intake of the chow and the high fat diet for sedentary (SED), running-wheel (RW), activity-based anorexia (ABA) and body weight matched (BWM) groups. Data are presented as mean ± SE.

Figure 6

Cognition tests. (A) percentage time spent exploring the novel and the familiar object during the recollection trial of the novel object recognition test. (B) percentage time spent exploring the novel and the familiar place object during the recollection trial of the novel place recognition test. (C) latency to enter the escape hole during the Barnes maze test, and (D) time spent exploring target, quadrats left to target (left), opposite of target (opposite) and right to target (right) of the Barnes maze during the probe trial of the Barnes maze test by sedentary (SED), and activity-based anorexia (ABA) groups. * indicates a significant difference between time spent with the familiar and the novel object p≤0.05.