Assessing Activity-based Anorexia in Mice.

Rodents develop activity-based anorexia (ABA) when exposed to a restricted feeding schedule and allowed free access to a running wheel. These conditions lead to a life-threatening reduction in body weight. However, rodents exposed to only one of these conditions ultimately adapt to re-establish normal body weight. Although increased running coupled with reduction in voluntary food intake appear paradoxical under ABA conditions, ABA behavior is observed across numerous mammalian species. The ABA paradigm provides an animal model for anorexia nervosa (AN), an eating disorder with severe dysregulation of appetite-behavior. Subjects are singly housed with free access to a running wheel. Each day, the subject is offered food for a limited amount of time. During the course of the experiment, a subject's body weight decreases from high activity and low caloric intake. The duration of the study varies based on how long food is offered daily, the type of food offered, the strain of mouse, if drugs are being tested, and environmental factors. A lack of effective pharmacological treatments for AN patients, their low quality of life, high cost of treatment, and their high mortality rate indicate the urgency to further research AN. We provide a basic outline for performing ABA experiments with mice, offering a method to investigate AN-like behavior in order to develop novel therapies. This protocol is optimized for use in Balb/cJ mice, but can easily be manipulated for other strains, providing great flexibility in working with different questions, especially related to genetic factors of ABA.

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation.

RATIONALE: Serotonin-1B receptor (5-HT1BR) agonist treatment induces obsessive-compulsive disorder (OCD)-like behaviors including locomotor stereotypy, prepulse inhibition deficits, and delayed alternation disruptions, which are selectively prevented by clinically effective OCD treatment. However, the role of 5-HT1BRs in modulating other repetitive behaviors or OCD-like patterns of brain activation remains unclear. OBJECTIVES: We assessed the effects of 5-HT1BR agonism on digging, grooming, and open field behaviors in mice. We also quantified effects on neuronal activation in brain regions overactivated in OCD. Finally, we assessed whether effects of the 5-HT1BR challenge could be blocked by clinically effective, but not ineffective, drug treatments. METHODS: Mice were tested in open field, dig, and splash tests after acute treatment with saline, 1, 3, 5, or 10 mg/kg RU24969 (5-HT1B/1A agonist). Behavioral effects of RU24969 were also tested following co-treatment with vehicle, 1 mg/kg WAY100635 (5-HT1A antagonist) and 5 or 10 mg/kg GR127935 (5HT1B/D antagonist). Separate mice were behaviorally assessed following chronic pretreatment with vehicle with 10 mg/kg fluoxetine or 20 mg/kg desipramine and acute treatment with saline or 10 mg/kg RU24969. Brains were analyzed for Fos expression in the orbitofrontal cortex, the dorsal striatum, and the cerebellum. RESULTS: RU24969 induced robust locomotor stereotypy and decreased rearing, digging, and grooming. Effects were blocked by GR127935 but not by WAY100635. RU24969 also increased Fos expression in the dorsal striatum. Chronic fluoxetine, but not desipramine, alleviated 5-HT1BR-induced effects. CONCLUSIONS: We report novel 5-HT1BR-induced behaviors and striatal activation that were alleviated only by clinically effective pharmacological OCD treatment. Studying the mechanisms underlying these effects could provide insight into OCD pathophysiology.