Physiology & Behavior 228 (2021) 113194 Available online 1 October 2020 0031-9384/© 2020 Elsevier Inc. All rights reserved. Mid-adolescent stress differentially affects binge-like intake of sucrose across estrous cycles in female rats ✰ Steven J. Lamontagne a , Meaghan M. Wilkin a , Janet L. Menard a, b , Mary C. Olmstead a, b, * a Department of Psychology, Queen’s University, Kingston, Ontario, Canada, K7L 3N6 b Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, K7L 3N6 A R T I C L E INFO Keywords: Binge eating disorder Compulsivity Elevated plus maze Reward Sex differences Sugar addiction ABSTRACT Binge eating disorder (BED), characterized by excessive food consumption within a discrete period of time, is the most prevalent of all eating disorders, with higher rates in women than men. Chronic stress, particularly during adolescence, is a significant risk factor for BED in women, but the mechanism underlying this relationship re- mains elusive. We investigated the phenomenon by testing the impact of mid-adolescent intermittent physical stress (IPS) on binge-like intake of sucrose in adult female rats, assessing how the behavior changed across reproductive cycles. One hundred and nineteen Long-Evans rats were exposed to IPS (n = 59) or no stress (NS; n = 60) for 12 days during mid-adolescence (PD35–46). Binge-like eating was induced in adult animals using an intermittent access protocol: animals were provided with 12 h or 24 h access to sucrose, 12 h access to saccharin, or 12 h access to food over 28 days. After 1- or 28-day abstinence, compulsive responding for sucrose was measured using a conditioned suppression paradigm. Rats given 12 h access to sucrose developed binge-like intake, measured as increased consumption during the first hour; the effect was magnified in IPS animals and most pronounced during proestrous. Solution intake in IPS rats was predicted by open arm entries in the elevated plus maze, suggesting that increased risk-taking behavior is associated with greater binge-like eating. IPS blocked conditioned suppression after 28 days of abstinence, pointing to a role of mid-adolescent stress in compulsivity. Collectively, these findings emphasize the impact of stress on the emergence of binge eating in females and suggest that intervention programs for women with a history of adolescent adversity should be investigated as a means to reduce risk for BED. 1. Introduction Binge eating, defined as excessive consumption of food within a discrete period of time, is a common characteristic of many eating dis- orders and the defining feature of binge eating disorder (BED) [31]. Compulsivity is also a primary characteristic of BED with affected in- dividuals displaying loss of control over food intake during binge epi- sodes. The most prevalent of all eating disorders [55], BED affects up to 3% of the general population [50] and is comorbid with a number of psychiatric and medical conditions (for review, see [1]). As with many mental health conditions, the incidence of BED is higher in females than males [55, 89], matching preclinical evidence for sex differences in binge-like eating [57], including a more rapid escalation of sugar [88] and fat [9] binge-like behavior in female rats. Stress plays a critical role in BED, both in the etiology of the disorder [78, 108] and in the precipitation of bingeing episodes [70]. For example, major life stressors, including trauma, abuse, bullying, and discrimination are significant risk factors for the development of BED [4, 39, 47, 95, 96], and negative moods associated with daily stressors are the most common trigger of binge eating [110] and eating in the absence of hunger [84]. In addition, binge-eating individuals rate lab-based stressors as more intense than do non-bingeing controls [46] and BED patients exhibit increased sensitivity to stressful life events [82]. Women appear to be particularly susceptible to binge eating following stress [23, 52], an effect that is mimicked in animal models [21]. The effect of stress on binge-like eating in rats is more pronounced during adolescence [45], fitting clinical evidence that this develop- mental stage is associated with increased vulnerability to stress-induced pathologies [85]. Adolescence, itself, can be parsed into different phases with unique neurodevelopmental profiles [15] and differential ✰ Conflict of Interest: The authors declare no competing financial or personal conflicts of interest related to this work. * Corresponding author at: Dept. of Psychology, 62 Arch St., Queens University, Kingston, ON, K7L 3N6. E-mail address: olmstead@queensu.ca (M.C. Olmstead). Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/physbeh https://doi.org/10.1016/j.physbeh.2020.113194 Received 28 July 2020; Received in revised form 14 September 2020; Accepted 29 September 2020