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Anorexia nervosa (AN) is a severe eating disorder affecting around 1 per 100 persons. However, the knowledge about its underlying pathophysiology is limited. To address the need for a better understanding of AN, an animal model was established early on in the late 1960's: the activity-based anorexia (ABA) model in which rats have access to a running wheel combined with restricted food access leading to self-starving/body weight loss and hyperactivity. Both symptoms, separately or combined, can also be found in patients with AN. The aim of this systematic review was to compile the current knowledge about this animal model as well as to address gaps in knowledge. Using the data bases of PubMed, Embase and Web of science 102 publications were identified meeting the search criteria. Here, we show that the ABA model mimics core features of human AN and has been characterized with regards to brain alterations, hormonal changes as well as adaptations of the immune system. Moreover, pharmacological interventions in ABA animals and new developments, such as a chronic adaptation of the ABA model, will be highlighted. The chronic model might be well suited to display AN characteristics but should be further characterized. Lastly, limitations of the model will be discussed.

Among the numerous consequences of prenatal alcohol exposure (PAE) is an increase in anxiety-like behavior that can prove debilitating to daily functioning. A significant body of literature has linked gestational day 12 (G12) heavy ethanol exposure with social anxiety, evident in adolescent males and females. However, the association between non-social anxiety-like behavior and moderate alcohol exposure, a more common pattern of drinking in pregnant women, is yet unidentified. To model moderate PAE (mPAE), we exposed pregnant Sprague-Dawley rats to either room air or vaporized ethanol for 6 h on G12. Adolescent offspring were then tested on postnatal days (P) 41-47 in one of the following four anxiety assays: novelty-induced hypophagia (NIH), elevated plus maze (EPM), light-dark box (LDB) and open-field (OF). Our findings revealed significant increases in measures of anxiety-like behavior in male PAE offspring in the NIH, LDB and OF, with no differences observed in females on any test. Additionally, male offspring who demonstrated heightened anxiety-like behavior as adolescents demonstrated decreased anxiety-like behavior in adulthood, as measured by a marble-burying test (MBT), while females continued to be unaffected in adulthood. These results suggest that mPAE leads to dynamic changes in anxiety-like behavior exclusively in male offspring.

Regulatory systems required to maintain behavioral arousal remain incompletely understood. We describe a previously unappreciated role that toll-like receptor 2 (Tlr2, a membrane bound pattern recognition receptor that recognizes specific bacterial, viral, and fungal peptides), contributes toward regulation of behavioral arousal. In 4–4.5 month old mice with constitutive loss of Tlr2 function (Tlr2−/− mice), we note a marked consolidation in the circadian pattern of both active and inactive states. Specifically, Tlr2−/− mice demonstrated significantly fewer but longer duration active states during the circadian dark cycle, and significantly fewer but longer duration inactive states during the circadian light cycle. Tlr2−/− mice also consumed less food and water, and moved less during the circadian light cycle. Analysis of circadian rhythms further suggested that Tlr2−/− mice demonstrated less day-to-day variability in feeding, drinking, and movement behaviors. Reevaluation of this same mouse cohort at age 8–8.5 months revealed a clear blunting of these differences. However, Tlr2−/− mice were still noted to have fewer short-duration active states during the circadian dark cycle, and continued to demonstrate significantly less day-to-day variability in feeding, drinking, and movement behaviors. These results suggest that Tlr2 function may have a role in promoting transitions between active and inactive states. Prior studies have demonstrated that Tlr2 regulates sickness behaviors including hypophagia, hyperthermia, and decreased activity. Our work suggests that Tlr2 function also evokes behavioral fragmentation, another aspect of sickness behavior and a clinically significant problem of older adults.

Centrally acting oxytocin (OT) is known to terminate food consumption in response to excessive stomach distension, increase in salt loading, and presence of toxins. Hypothalamic-hindbrain OT pathways facilitate these aspects of OT-induced hypophagia. However, recent discoveries have implicated OT in modifications of feeding via reward circuits: OT has been found to differentially affect consumption of individual macronutrients in choice and no-choice paradigms. In this mini-review, we focus on presenting and interpreting evidence that defines OT as a key component of mechanisms that reduce eating for pleasure and shape macronutrient preferences. We also provide remarks on challenges in integrating the knowledge on physiological and pathophysiological states in which both OT activity and macronutrient preferences are affected.

Neural circuits distributed within the brainstem, hypothalamus, and limbic forebrain interact to control food intake and energy balance under normal day-to-day conditions, and in response to stressful conditions under which homeostasis is threatened. Experimental studies using rats and mice have generated a voluminous literature regarding the functional organization of circuits that inhibit food intake in response to satiety signals, and in response to stress. Although the central neural bases of satiation and stress-induced hypophagia often are studied and discussed as if they were distinct, we propose that both behavioral states are generated, at least in part, by recruitment of two separate but intermingled groups of caudal hindbrain neurons. One group comprises a subpopulation of noradrenergic (NA) neurons within the caudal nucleus of the solitary tract (cNST; A2 cell group) that is immunopositive for prolactin-releasing peptide (PrRP). The second group comprises non-adrenergic neurons within the cNST and nearby reticular formation that synthesize glucagon-like peptide 1 (GLP-1). Axonal projections from PrRP and GLP-1 neurons target distributed brainstem and forebrain regions that shape behavioral, autonomic, and endocrine responses to actual or anticipated homeostatic challenge, including the challenge of food intake. Evidence reviewed in this article supports the view that hindbrain PrRP and GLP-1 neurons contribute importantly to satiation and stress-induced hypophagia by modulating the activity of caudal brainstem circuits that control food intake. Hindbrain PrRP and GLP-1 neurons also engage hypothalamic and limbic forebrain networks that drive parallel behavioral and endocrine functions related to food intake and homeostatic challenge, and modulate conditioned and motivational aspects of food intake.