Development an pharmacological characterization of models of binge eating in laboratory animals

Introduction and aim of the studies: Binge eating disorder (BED) is a more recently defined syndrome that features recurrent episodes of overeating, without inappropriate compensatory behaviors. The development of an animal model is an important step for understanding the aetiology of BED, and for developing effective treatments. Most importantly, the utility of an animal model lies in its face validity or embodiment of the characteristics prevalent in clinical populations. During my studies I worked to reproduce two animal models of binge eating described in literature: 1) Key synergistic role of past caloric restriction and stress; 2) Contrast-induced cycling: consummatory and emotional dependence on preferred food. A model of intermittent excessive behavior. and to develop two new animal models of binge eating with the pharmacological characterization: 3) Exposure to environmental-food associated cues elicited compulsive behavioural response to actively obtain food rewards in female rats; 4) Exposure to food related cues induced overeating in female rats exposed to cyclic dieting 5) I studied also the susceptibility of congenic DA.WOKW rats to develop binge eating as possible model to elucidate the genetics of binge eating disorder. Results: 1) We were able to obtain binge eating by combining repeated caloric restrictions and electric foot-shock stress only in msP rats with maternal separation. This animal study might support the clinical hypothesis that severe stress during childhood leads to vulnerability to abnormal eating behavior in response to stress in later life in humans. 2) The present study failed to replicate the work by Cottone and co-workers. In particular we have not been able to detect significant difference in body weight gain between control and High-Palatable food exposed rats. To investigate the reasons of these discrepancies would require a detailed analysis of several variables. We decided, therefore, to develop an alternative model to use for drug test purposes. 3) This model used was developed exploiting food cues-induced overeating under operant self-administration condition. Prior presentation of cues predictive of food reward engage the animal into a food-seeking state resulting in overfeeding occurring at beginning of the food delivery session. This increase of responding over baseline condition may reflect an increased “craving” for food resulting in loss of control reaction to food cues. Rimonabant and Sibutramine reduced food intake in both cue-preexposed and nonpreexposed rats suggesting a general inhibition of appetitive behaviour following drug administrationof these drugs. Fluoxetine and Topiramate, on the other hand, more potently affected food self-administration in cue preexposed rats. This effect is indicative of a more selective action of these compound in the regulation of food-seeking behaviour rather than in the control of satiety mechanisms. 4) In this model electric foot-shock of Hagan’s model was substituted with a different stress, related to lack of control over environmental circustances induced by allowing rats to see and to smell the palatable food but preventing them from access to it for 15 min. We obtained a clear binge eating response in rats that was confirmed for all the experiments. In this model the treatment with fluoxetine (3 mg/Kg) is able to reduce HP food intake in the group of R + P and not in NR + NP showing a specific effect in reducing the loss of control in overeating after the pre-exposure to HP food with a history of restriction. 5) DA.WOKW 16, DA.WOKW 5a, and DA.WOKW 3a, did not develop binge eating while DA, WOKW and DA.WOKW 3b developed binge eating. It will be necessary more studies to well correlate these genetics results and behavioural studies. Conclusion: The development of this animal model of binge eating should prove useful in identifying and assessing further critical enviromental triggers and specific physiological changes that precipitate and maintain the behavior and eventually, in guiding better prevention and treatment strategies for binge eating disorders.