Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

Gelegen, Çiğdem; Pjetri, Eneda; Campbell, Iain C.; Collier, David; Oppelaar, Hugo; Kas, Martien

doi:10.1016/j.euroneuro.2009.10.001

Cited by 24 publications

(24 citation statements)

References 79 publications

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“…We therefore identified an appropriate mouse strain with which to perform ABA studies. Mouse strain differences in susceptibility to ABA have been reported previously, with the A/J and DBA/2J strains showing increased susceptibility to developing the ABA phenotype compared with C57BL/6J mice (Gelegen et al, 2007(Gelegen et al, , 2008(Gelegen et al, , 2010. In fact, C57BL/6J mice do not develop ABA, but instead show reductions in wheel running during food restriction.…”

Section: Discussionmentioning

confidence: 75%

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Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice

Klenotich

Seiglie

McMurray

et al. 2012

Neuropsychopharmacol

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Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10 h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6 h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12 mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18 mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN.

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Section: Discussionmentioning

confidence: 75%

“…We first performed a strain comparison study to identify a mouse strain with high vulnerability to ABA, because mice show strain differences in ABA susceptibility (Gelegen et al, 2007(Gelegen et al, , 2008(Gelegen et al, , 2010. We then optimized ABA experimental parameters for investigating drug treatment effects in mice.…”

Section: Introductionmentioning

confidence: 99%

Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice

Klenotich

Seiglie

McMurray

et al. 2012

Neuropsychopharmacol

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“…In support of this view, pre-existing conditions of anxiety and over-exercise are common among individuals with anorexia nervosa (Dellava et al, 2010). Similarly, mice carrying genes that elevate trait anxiety exhibit stronger hyperactivity when stressed (Gelegen et al, 2007; Gelegen et al, 2010). Moreover, results from animal models indicate that exercise can be anxiolytic (Sciolino and Holmes, 2012) and stress-relieving (Schoenfeld et al, 2013) through the production of BDNF (brain-derived neurotrophic factor) (Hill and Martinowich, 2015; Rasmussen et al, 2009).…”

Section: Anorexia Nervosamentioning

confidence: 99%

Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

Aoki¹,

Chowdhury²,

Wable³

et al. 2017

Brain Research

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Anorexia nervosa is a mental illness that emerges primarily during early adolescence, with mortality rate that is 200 times higher than that of suicide. The illness is characterized by intense fear of gaining weight, heightened anxiety, obstinate food restriction, often accompanied by excessive exercise, in spite of mounting hunger. The illness affects females nine times more often than males, suggesting an endocrine role in its etiology. Its relapse rate exceeds 25%, yet there are no accepted pharmacological treatments to prevent this. Here, I summarize studies from this laboratory that have used adolescent female rodents in activity-based anorexia (ABA), an animal model of anorexia nervosa, with the goal of identifying neurobiological underpinnings of this disease. We put forth a hypothesis that a GABAergic mechanism within the hippocampus is central to regulating an individual’s anxiety which, in turn, strongly influences the individual’s resilience/vulnerability to ABA. In particular, we propose that ionotropic GABAA receptors containing the subunits alpha4 and delta, are at play for exerting shunting inhibition upon hippocampal pyramidal neurons that become more excitable during ABA. Since these receptors confer insensitivity to benzodiazepines, this pharmacological profile of ABA fits with lack of report indicating efficacy of benzodiazepines in reducing the anxiety experienced by individuals with anorexia nervosa. The idea that the GABAergic system of the hippocampus regulates resilience/vulnerability to anorexia nervosa complements current opinions about the important roles of the prefrontal cortex, amygdala, striatum, gustatory pathways and feeding centers of the hypothalamus and of the neuromodulators, serotonin and dopamine, in the etiology of the disease.

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“…The range of body weight loss in ABA appears to be between 10% and 30% of the body weight before ABA [18, 19]. Thus, one could define whether an animal is susceptible to ABA if their final body weight is below a specific threshold percent of their initial body weight, such as 75% [20].…”

Section: Introductionmentioning

confidence: 99%

“…There is large variability between mouse strains in body weight loss during ABA [18, 24, 25]. Studies in female mice and rats indicate that RW activity during ad-libitum feeding predicts body weight loss during ABA [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

Perez‐Leighton

Grace

Billington

et al. 2014

Physiology & Behavior

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Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement can promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN.

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Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

Cited by 24 publications

References 79 publications

Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice

Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice

Synaptic changes in the hippocampus of adolescent female rodents associated with resilience to anxiety and suppression of food restriction-evoked hyperactivity in an animal model for anorexia nervosa

Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

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