Effect of chronic administration of tamoxifen and/or estradiol on feeding behavior, palatable food and metabolic parameters in ovariectomized rats

Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer; however many women complain of weight gain during TAM treatment. The anorectic effects of estradiol (E) and TAM are well known, although the effects of E on the consumption of palatable food are controversial and there is no information regarding the effects of TAM on palatable food consumption. The aim of this study was to investigate the effects of chronic treatment with estradiol and/or tamoxifen on feeding behavior in ovariectomized rats exposed to standard chow and palatable foods (Froot Loops® or chocolate). Additionally, parameters such as body weight, uterine weight, lipid profile and plasma glucose were also measured. Wistar rats were ovariectomized (OVX) and subsequently injected (ip.) for 40 days with: E, TAM, E+TAM or vehicle (OVX and SHAM - controls). Behavioral tests were initiated 25 days after the start of treatment. Froot Loops® consumption was evaluated in a novel environment for 3 min. Standard chow intake was evaluated for two days and chocolate intake for 7 days in the home cage in a free choice model (chocolate or standard chow). Rats injected with E, TAM and E+TAM groups showed a reduction in body weight and standard chow intake, compared with control groups. With regard to palatable food intake, the E, TAM and E+TAM groups demonstrated increased consumption of Froot Loops®, compared with the SHAM and OVX groups. In contrast, all groups increased their consumption of chocolate, compared with standard chow; however the E group consumed more chocolate than the OVX, TAM and E+TAM groups. Despite these differences in chocolate consumption, all groups showed the same caloric intake during the chocolate exposure period; however the TAM and E+TAM groups presented decreased body weight. Treatment with estradiol and tamoxifen showed a favorable lipid profile with low levels of TC, LDL, LDL/HDL ratio and lower levels of plasma glucose. The E group presented high levels of TG and HDL, when compared with the TAM and E+TAM groups. Taken together, results suggest that TAM acted in an estrogen-like manner on the majority of parameters analyzed. However, tamoxifen acts in a different manner depending on the type of palatable food and the exposure. In addition, the TAM group demonstrated weight loss, compared with other groups independently of the type of food presented (palatable food or standard chow), showing a low caloric efficiency.