The ovarian cycle has profound effects on food intake in a variety of species, including humans. This effect is very prominent in female rats which display a 20 - 40 percent decrease in food intake during the estrous (sexually receptive) phase of the cycle. This decline in food intake during estrus appears to be mediated, at least in part, by increased sensitivity to the satiety effects of cholecystokinin (CCK), a gut peptide that is released during meals and functions to decrease food intake by generating a satiety signal that is relayed to the brain via the vagus nerve. The importance of the rat's ovarian cycle in the control of food intake is revealed by ovariectomy, which increases food intake, decreases sensitivity to CCK, promotes body weight gain and, in the absence of estrogen replacement, induces obesity. Although the decline in estrogen activity appears to mediate the hyperphagia and associated body weight gain following ovariectomy, it is not known whether changes in endogenous estrogen activity mediate the decrease in food intake and increase in CCK satiation expressed during estrus in cycling rats. One goal of this proposal is to determine whether antagonism of central estrogen receptor activity will block the estrous-related decrease in food intake and increase in CCK satiation. To investigate this hypothesis, food intake and meal patterns will be monitored in cycling rats treated with an antiestrogen at various phases of the estrous cycle. A second goal is to use c-Fos immunocytochemistry, a marker of neuronal activity, to determine whether increased sensitivity to the satiety effects of CCK during estrus is mediated by increased responsivity of neurons that process satiety signals generated by consumption of a meal and by injection of CCK. A third goal of this proposal is to determine the brain areas where endogenous estrogen acts to decrease food intake and increase CCK satiation during estrus. In this experiment, in situ hybridization and immunocytochemistry techniques will be combined to determine whether those neurons that are activated by CCK express estrogen receptors. Together, these studies have the potential to broaden our understanding of the mechanism by which food intake is controlled across the estrous cycle of female rats. Because eating disorders are more prevalent in women than in men, this proposal targets an important research question with clear clinical relevance .

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
1R03MH063932-01A2
Application #
6674692
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Winsky, Lois M
Project Start
2003-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$73,000
Indirect Cost
Name
Florida State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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Rivera, Heidi M; Eckel, Lisa A (2010) Activation of central, but not peripheral, estrogen receptors is necessary for estradiol's anorexigenic effect in ovariectomized rats. Endocrinology 151:5680-8
Santollo, Jessica; Eckel, Lisa A (2008) The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle. Physiol Behav 93:842-50
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Messina, Michelina M; Boersma, Gretha; Overton, J Michael et al. (2006) Estradiol decreases the orexigenic effect of melanin-concentrating hormone in ovariectomized rats. Physiol Behav 88:523-8
Rivera, Heidi M; Eckel, Lisa A (2005) The anorectic effect of fenfluramine is increased by estradiol treatment in ovariectomized rats. Physiol Behav 86:331-7
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
Atchley, Deann P D; Weaver, Karen L; Eckel, Lisa A (2005) Taste responses to dilute sucrose solutions are modulated by stage of the estrous cycle and fenfluramine treatment in female rats. Physiol Behav 86:265-71
Eckel, Lisa A (2004) Estradiol: a rhythmic, inhibitory, indirect control of meal size. Physiol Behav 82:35-41