1. Estradiol’s Effects on Appetite for Palatable Substances and Alcohol Intake in Female Rats Jessica Fitch, Brian Gentile, Karen Boswell, Larry Reid, & Meta Reid

2. Introduction  The effects of Estradiol, a form of the female hormone estrogen, have been studied in rats. A single pharmacologically effective dose has both short- and long-term effects on rats’ ingestion behaviors. Introduction  In Reid’s laboratory at RPI, a series of studies examined the effects of estradiol valerate (EV) on rats’ consumption of alcoholic beverage.  In adult female rats, the short-term effects include a decrease in alcohol intake and a loss of body weight.  Subsequently, rats regain the lost weight and their intake of alcoholic beverage is dramatically increased.

4.  These effects have been hypothesized to be related to beta-endorphin activity.  Specifically, it is believed that adaptation to estradiol leads to a heightened sensitivity of the opioid system. A substantial body of research demonstrates that increased opioid activity is associated with increases in consumption of alcohol and also in excess intake of palatable foods (e.g., sweets).  Such findings have implications for theories of alcoholism, eating disorders, and for women’s health (e.g., estradiol is prescribed for estrogen replacement therapy).

5. Saccharin study: Spring 2002 Experimental Design: 20 rats were randomly assigned to receive a 2.0 mg/rat injection of EV (about 10 mg/kg), and 20 received placebo. Within each of the above groups, 10 were randomly assigned to receive access to a high concentration saccharin solution, and 10 had access to a low concentration solution. During the weeks in which rats had opportunity to drink saccharin, it was available for 4 consecutive days (Tuesday through Friday) for 2 hours, immediately following lights off. The study spanned more than 90 days.

6. Saccharin intake: In general, rats drank considerably more of the low concentration saccharin. Intake of the high concentration solution was quite low for both groups throughout the course of the study. There were differences between EV and placebo groups: For the high concentration, EV rats consumed less solution than placebo rats. For the low concentration, no differences were observed during the first two weeks. However, after that EV rats tended to take more solution than placebo rats.

8. Rats treated with EV consumed less of the unpleasant-tasting high concentration saccharin solution than placebo-treated rats. Conversely, EV rats consumed the palatable low concentration solution more avidly than placebo rats. Results for the low concentration parallel those seen in the alcohol studies, where EV-injected rats consumed more of a sweetened ethanol solution than placebo rats. Conclusions from Saccharin study

9. Intake of Complex Ingesta Dose-response studies assessing EV’s effects on intake of chocolate cake batter

10. During the past year, we have assessed rats’ intake of cake batter: a complex, palatable food. EV-treated rats do not eat more lab chow than placebo-treated rats. But lab chow is not especially palatable… Would EV-treated rats consume more cake batter than placebo-treated rats? On the basis of results from the ethanol and saccharin studies, we expected intake of cake batter to be higher for the EV rats.

11.  The basic procedure involves injecting rats with a dose of EV or placebo, waiting about one week, and then providing opportunity to eat cake batter (for a series of 4 days or 8 days).  The measures of interest are the amounts of batter consumed daily, and body weights.  Doses have ranged from 10 mg/kg to 0.09 mg/kg

14. Total intakes of chocolate cake mix batter taken across an 8- day period. The n for placebo is 15. The n for each of the other groups is 8. The mean intake in terms of grams of batter taken for the group receiving 0.375 mg of EV/kilogram of bodyweight during the 8 days was 203.4 grams, which is nearly the mean weight of the females (217 grams) at beginning of the 8 days of opportunity to take batter. In other words, the EV treated females took nearly their weight in batter during an 8-day period of opportunity to do so (over 10% of their bodyweight daily).

15. Conclusions Female rats eat a lot of chocolate cake batter, and EV enhances appetite for batter. This effect persists over weeks, especially at the higher doses. The effect of EV is detected at doses low enough to be of possible relevance to human women’s health.

16. Implications and Speculation Do these results have any implications for women’s health? Estradiol is often prescribed for menopausal women. Millions of women take estradiol for purposes of birth control.Could elevated levels or estradiol, or adaptation to estradiol, affect appetitive behavior in ways that increase the risk of alcohol abuse ? Obesity?

17. …and Future Directions Would long-term access to batter lead to excessive weight gain? Trends in our data suggest it would. Will low doses of EV enhance intake of ethanol? Studies planned for this summer will address these questions.