Research Interest

• Neuroendocrine control of ingestive behavior
• ovarian rhythms in behavior
• activity-based anorexia
• serotonergic control of feeding

Current Research

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.

Publications

• Rivera HM, Oberbeck DR, Kwon B, Houpt TA, Eckel LA. Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats. Brain Res. 1259:51-8. (2009) PDF
• Santollo J, Eckel LA. Effect of a putative ERalpha antagonist, MPP, on food intake in cycling and ovariectomized rats. Physiol Behav. 97(2):193-8. (2009)
• Santollo J, Eckel LA. The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle. Physiol Behav. 93(4-5):842-50. (2008)
• Santollo J, Eckel LA. Estradiol decreases the orexigenic effect of neuropeptide Y, but not agouti-related protein, in ovariectomized rats. Behav Brain Res. 191(2):173-7. (2008)
• Maner JK, Miller SL, Schmidt NB, Eckel LA. Submitting to defeat: social anxiety, dominance threat, and decrements in testosterone. Psychol Sci. 19(8):764-8. (2008)
• O'Leary MM, Loney BR, Eckel LA. Gender differences in the association between psychopathic personality traits and cortisol response to induced stress. Psychoneuroendocrinology. 32(2):183-91. (2007)
• Blackhart GC, Eckel LA, Tice DM. Salivary cortisol in response to acute social rejection and acceptance by peers. Biol Psychol. 75(3):267-76. (2007)
• Sachs-Ericsson N, Burns AB, Gordon KH, Eckel LA, Wonderlich SA, Crosby RD, Blazer DG. Body mass index and depressive symptoms in older adults: the moderating roles of race, sex, and socioeconomic status. Am J Geriatr Psychiatry. 15(9):815-25. (2007)
• Santollo J, Wiley MD, Eckel LA. Acute activation of ER alpha decreases food intake, meal size, and body weight in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol. 293(6):R2194-201. (2007)
• Loney BR, Butler MA, Lima EN, Counts CA, Eckel LA. The relation between salivary cortisol, callous-unemotional traits, and conduct problems in an adolescent non-referred sample. J Child Psychol Psychiatry. 47(1):30-6. (2006)
• Atchley DP, Eckel LA. Treatment with 8-OH-DPAT attenuates the weight loss associated with activity-based anorexia in female rats. Pharmacol Biochem Behav. 83(4):547-53. (2006)
• Messina MM, Boersma G, Overton JM, Eckel LA. Estradiol decreases the orexigenic effect of melanin-concentrating hormone in ovariectomized rats. Physiol Behav. 88(4-5):523-8. (2006)
• Becker JB, Arnold AP, Berkley KJ, Blaustein JD, Eckel LA, Hampson E, Herman JP, Marts S, Sadee W, Steiner M, Taylor J, Young E. Strategies and methods for research on sex differences in brain and behavior. Endocrinology. 146(4):1650-73. (2005)
• Eckel LA, Rivera HM, Atchley DP. The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats. Am J Physiol Regul Integr Comp Physiol. 288(6):R1486-91. (2005)
• Atchley DP, Eckel LA. Fenfluramine treatment in female rats accelerates the weight loss associated with activity-based anorexia. Pharmacol Biochem Behav. 80(2):273-9. (2005)
• Rivera HM, Eckel LA. The anorectic effect of fenfluramine is increased by estradiol treatment in ovariectomized rats. Physiol Behav. 86(3):331-7. (2005)
• Atchley DP, Weaver KL, Eckel LA. Taste responses to dilute sucrose solutions are modulated by stage of the estrous cycle and fenfluramine treatment in female rats. Physiol Behav. 86(3):265-71. (2005)
• Eckel LA, Moore SR. Diet-induced hyperphagia in the rat is influenced by sex and exercise. Am J Physiol Regul Integr Comp Physiol. 287(5):R1080-5. (2004)
• Eckel LA. Estradiol: a rhythmic, inhibitory, indirect control of meal size. Physiol Behav. 82(1):35-41. (2004)