Abstract
The ovarian hormone estradiol plays an important role in the control of food intake in the female rat. For example, ovariectomized (OVX) rats display hyperphagia and excessive weight gain in the absence of estradiol replacement and ovarian-intact rats display an estrous-related decrease in food intake. Estradiol’s ability to decrease food intake appears to be indirect. Several groups have demonstrated that estradiol increases the hypophagic effect of cholecystokinin (CCK), a gut peptide implicated in the physiological control of meal size. Because the involvement of CCK cannot entirely account for the hypophagic effect of estradiol, other peptide or neurotransmitter systems may participate in the estrogenic control of food intake. The goal of this thesis was to investigate the hypothesis that estradiol may interact with the serotonin (5-HT) system to inhibit food intake in the female rat. In two studies, food intake was monitored in male and female rats (Study 1), and in OVX rats with and without estradiol replacement (Study 2), following acute administration of fenfluramine (FEN), a serotonin (5-HT) receptor agonist that has been used extensively to investigate the contribution of endogenous 5-HT to the control of food intake. Study 1 demonstrated that FEN-induced anorexia was sexually dimorphic and varied across the estrous cycle. Both the magnitude and duration of FEN-induced anorexia was greater in female rats, relative to male rats. The magnitude of FEN-induced anorexia was also greater in estrous rats, relative to diestrous rats. Thus, FEN-induced anorexia appears to be modulated by gonadal hormone status. These effects may be mediated by estradiol since female rats have higher levels of estradiol than male rats and because estradiol secretion is increased prior to estrus. Study 2 was designed as a direct test of this hypothesis. The results of Study 2 demonstrated that FEN-induced anorexia was greater in estradiol-treated OVX rats, relative to oil-treated OVX rats. Thus, FEN-induced anorexia is modulated by estradiol treatment in OVX rats. Together, my findings indicate that both endogenous and exogenous estradiol increases FEN-induced anorexia. Because FEN increases 5-HT neurotransmission, my data suggest that estradiol interacts with the 5-HT system to decrease meal size in female rats.
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