Effects of 2-hydroxyestradiol on binge eating in rats
Open Access
- Author:
- Babbs, Richard K
- Graduate Program:
- Physiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 14, 2012
- Committee Members:
- Rebecca L Corwin, Dissertation Advisor/Co-Advisor
Rebecca L Corwin, Committee Chair/Co-Chair
Erica Unger, Committee Member
John E Hayes, Committee Member
Barbara Jean Rolls, Committee Member - Keywords:
- binge
2-hydroxyestradiol
sex differences
rat
eating disorders - Abstract:
- One conundrum of binge eating is that women are more likely to suffer from binge-related eating disorders, even though estradiol decreases food intake. 2-hydroxyestradiol (2OHE2), an estrogen metabolite, may account for the contradiction, due to possible interference with dopamine (DA) signaling. Therefore, a series of studies was conducted in order to investigate the effects of 2OHE2 on binge eating in an established rat model. Research presented in Chapter 2 investigated the acute effects of 2OHE2 on bingeing. Two cohorts (1 male, 1 female) of 34 non-food-deprived rats were each separated into two groups: 1) daily control (D) (received an optional source of dietary fat for 20 min every day) or 2) bingeing (INT) (received fat intermittently, i.e. 20 min on Mon, Weds, Fri). During the 5-week binge induction period, shortening intakes escalated over the 5-week binge induction period significantly faster in females than in males, such that males consumed significantly less fat relative to body mass than did females after 5 weeks. This result is consistent with the idea that biological differences contribute to sex differences in bingeing. Rats of both sexes were then injected with 2OHE2 (1.0, 3.0, and 10.0 μg/kg intraperitoneally), vehicle, or 2-methoxyestradiol (2ME2) immediately prior to fat access. Fat intake was significantly stimulated by 2OHE2 only in the INT rats (p<0.03). Furthermore, this effect seemed to be more subtle in females than in males. The results indicate that 2OHE2 can acutely exacerbate intake in a bingeing rat. Additionally, results suggest that females may escalate intakes faster due to endogenous hormones. Research presented in Chapter 3 investigated the effects of chronic administration of 2OHE2 on bingeing, and the effect of 2OHE2 on DA efflux in the prefrontal cortex (PFC) of bingeing rats. In study 1, three groups of female rats (n=16 per group) were used. Group one was ovariectomized (OVX) and implanted with an osmotic mini-pump containing 2OHE2 (E); group two underwent OVX surgery and received a vehicle implant (O); group three underwent sham surgery and received a vehicle implant (I). All rats were exposed to the INT protocol described above. After four weeks, shortening intake escalated more quickly in the E rats than in either the O or I rats. Additionally, during week 4, E rats ate significantly more shortening than did I rats, and significantly less chow than either O or I rats. The results indicate that 2OHE2 can exacerbate binge escalation and shift intake from more homeostatically-driven eating to more hedonic eating. In study 2, male rats (n=6) were exposed to a minimum of 5 weeks of the INT protocol before they were implanted with a microdialysis guide cannula targeting the PFC. DA efflux was recorded before, during, and after presentation of shortening and intraperitoneal injection of either 2OHE2 (3.0 μg/kg) or vehicle. 2OHE2 abolished the shortening-evoked DA efflux that was present after injection with vehicle, and significantly enhanced shortening intake. These results demonstrate that 2OHE2 can alter DA signaling in the PFC of bingeing rats. The results of the present studies indicate that 2OHE2 can exacerbate intake both acutely and chronically in a rat model of bingeing. These effects may due, in part, to the effects of 2OHE2 on DA signaling in the PFC. Together this suggests a novel mechanism explaining the increased risk for binge-related eating disorders in females.