- Neuroendocrine control of ingestive behavior
- ovarian rhythms in behavior
- activity-based anorexia
- serotonergic control of feeding
Role of Estradiol in the Control of Food Intake
A distinctive pattern of food intake and running wheel activity are apparent in female rats across the 4-day estrous cycle. During estrus, just after the peak in estradiol secretion, food intake is decreased 20-40% and running wheel activity is increased by over 100%. Both of these effects are abolished by surgical removal of the ovaries but they can be reinstated by estradiol replacement alone. Thus, the behavioral changes associated with estrus are mediated by estradiol.
The following figure from our lab illustrates the estrous-related changes in food intake and running wheel activity in a group of female rats. Abbreviations: D1; diestrus 1, D2; diestrus 2, P; proestrus, E; estrus.
In our lab we are using multiple approaches to investigate the mechanism by which estradiol controls food intake in female rats. Behavioral and pharmacological studies are designed to investigate the effects of estradiol and other satiety peptides on spontaneous feeding and locomotor activity in female rats. Immunohistochemical studies focus on the effects of estradiol on neuronal activity and peptide expression within brain regions that process feeding-stimulated signals. For example, using the induction of c-Fos-like immunoreactivity as a marker of neuronal activation, we have recently discovered that estradiol treatment in ovariectomized rats increases neuronal activity induced by feeding-related stimuli in multiple brain regions. Thus, estradiol may decrease food intake during estrus by increasing the central processing of peripherally generated satiety signals. The following illustration includes representative photomicrographs of feeding-stimulated c-Fos-like immunoreactivity in the nucleus of the solitary tract, a brain region implicated in the physiological control of food intake. Estradiol treatment significantly enhanced the amount of c-Fos expression (compare right panels with left panels) induced by 5 and 10 ml of milk consumption. Abbreviations: iNTS; intermediate nucleus of the solitary tract, IV; fourth ventricle, Veh; vehicle-treated rat, E2; estradiol-treated rat.
Finally, molecular studies focus on estradiol-mediated changes in gene expression. Currently, we are using in situ hybridization techniques to map the distribution of estrogen receptors in hindbrain regions involved in the physiological control of food intake. Future experiments will use expression profiling techniques to identify the phenotype of neurons that are regulated by estradiol.
Activity-Based Anorexia in Female Rats
Anorexia nervosa is a complex eating disorder characterized in part by hypophagia, disorganized eating patterns, body weight loss, hyperactivity, and a dysregulation of the hypothalamic-pituitary-gonadal axis. About 90% of clinically-diagnosed cases involve women. Therapeutic treatment of the symptoms of anorexia nervosa is limited due to our lack of understanding of the multiple factors that underlie this complex disorder.
Animal studies have shown that female rats maintained on a food restriction schedule and given free access to running wheels display hypophagia, rapid body weight loss, increased running wheel activity, and a disruption of the estrous cycle. This phenomenon has been labeled activity-based anorexia.
In our lab, we are using this animal model to investigate the physiological and neural mechanisms underlying anorexia nervosa. Currently, there are several ongoing projects.
- We are characterizing the behavioral profile of rats with activity-based anorexia by monitoring spontaneous feeding and activity patterns in rats prior to, during, and after the induction of activity-based anorexia. These studies are designed to screen for behavioral characteristics that may increase susceptibility to developing an eating disorder.
- Because anorexia nervosa is more prevalent in women than in men, we are examining the involvement of estradiol in the development and maintenance of activity-based anorexia.
- To investigate the neural mechanism underlying activity-based anorexia, we are examining the patterns of feeding-induced neuronal activation in rats with and without activity-based anorexia.