Weight restored anorexic women have increased serotonin (5-HT) activity compared to women that have never been diagnosed with an eating disorder. This suggests that increased 5-HT activity may be a pre-existing trait in women that develop anorexia nervosa and may contribute to the etiology of this disorder. To further investigate the role of 5-HT in anorexia, I will use the activity-based anorexia (ABA) paradigm, a rat model of anorexia nervosa that induces hyperactivity, hypophagia, weight loss, and a disruption of the ovarian reproductive cycle. Using this paradigm, I discovered that female rats treated with a 5-HT agonist developed the symptoms of ABA quicker than control rats. This proposal will test the central hypothesis that the serotonergic system modulates the expression of behavioral and physiological symptoms associated with ABA in female rats.
In Specific Aim 1, a 5-HT antagonist will be administered concurrently with exposure to the ABA paradigm to test the hypothesis that blockade of 5-HT activity decreases ABA.
In Specific Aim 2, a 5-HT2c receptor antagonist will be administered to rats subjected to the ABA paradigm to test the hypothesis that antagonism of this receptor subtype decreases ABA.
In Specific Aim 3, c-fos immunocytochemistry will be used to test the hypothesis that brain regions that control satiety are more sensitive to 5-HT in female rats with ABA compared to normal weight control rats.
Eckel, Lisa A; Rivera, Heidi M; Atchley, Deann P D (2005) 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:R1486-91 |