The ovarian hormone estradiol has profound effects on most, if not all, of the nervous system. As a result, estradiol influences a variety of physiological functions and,therefore, behavior. Among its varied actions, estradiol exerts a potent inhibitory effect on food intake that is expressed in a variety of species, including humans. In recent years, this action of estradiol has been linked to the development of eating disorders, as well as the increase in appetite and weight gain that is often observed in estradiol-deficient, postmenopausal women. A crucial first step in understanding how estradiol may contribute to either of these conditions is to determine how it affects the controls of food intake in healthy animals. Available evidence suggests that the inhibitory effect of estradiol on food intake is mediated by its ability to increase the strength of other key elements within the satiety-signaling system. Here, we propose to investigate several fundamental questions regarding the possible interaction of estradiol and serotonin (5-HT), one such satiety signal, in the control of food intake in the female rat.A combination of behavioral, pharmacological, antomical, and molecular techniques will be used to investigate our central hypothesis, which is that an increase in 5-HT neurotransmission mediates the anorectic effect of estradiol in the female rat.
In Specific Aims 1 and 2, we will establish brain regions that are both necessary and sufficient for the estrogenic inhibition of food intake.
In Specific Aim 3, we will determine whether increased activation of postsynaptic 5-HT2C receptors contributes to the estrogenic inhibition of food intake.
In Specific Aim 4, we will determine whether estradiol acts with the midbrain raphe system to increase the release and/or turnover of 5-HT within specific brain regions implicated in the control of food intake. Successful completion of these studies will broaden our understanding of the behavioral and neurobiological mechanisms underlying the anorectic effect of estradiol. Because our proposed studies focus on an interactive effect of estradiol and 5-HT in the control of food intake, and abnormalities in serotonergic function have been identified in women with anorexia nervosa, completion of this work has the potential to reveal how estradiol may function as a risk factor for eating- related disorders. Thus, this proposal targets an important research question with clear clinical relevance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK073936-05
Application #
8019610
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Hyde, James F
Project Start
2007-01-01
Project End
2013-12-31
Budget Start
2011-01-01
Budget End
2013-12-31
Support Year
5
Fiscal Year
2011
Total Cost
$243,099
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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Torregrossa, Ann-Marie; Nikonova, Larissa; Bales, Michelle B et al. (2014) Induction of salivary proteins modifies measures of both orosensory and postingestive feedback during exposure to a tannic acid diet. PLoS One 9:e105232
Santollo, J; Eckel, L A (2013) Oestradiol decreases melanin-concentrating hormone (MCH) and MCH receptor expression in the hypothalamus of female rats. J Neuroendocrinol 25:570-9
Loney, Gregory C; Torregrossa, Ann-Marie; Carballo, Chris et al. (2012) Preference for sucralose predicts behavioral responses to sweet and bittersweet tastants. Chem Senses 37:445-53
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Santollo, Jessica; Torregrossa, Ann-Marie; Eckel, Lisa A (2011) Estradiol acts in the medial preoptic area, arcuate nucleus, and dorsal raphe nucleus to reduce food intake in ovariectomized rats. Horm Behav 60:86-93
Loney, Gregory C; Torregrossa, Ann-Marie; Smith, James C et al. (2011) Rats display a robust bimodal preference profile for sucralose. Chem Senses 36:733-45
Santollo, Jessica; Katzenellenbogen, Benita S; Katzenellenbogen, John A et al. (2010) Activation of ERα is necessary for estradiol's anorexigenic effect in female rats. Horm Behav 58:872-7
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

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