Cyclic estradiol benzoate (EB) treatment models the endogenous cycle and maintains normal patterns of body weight gain, daily food intake, and spontaneous meal size in ovariectomized (OVX) rats. A: OVX increased and cyclic estradiol treatment normalized body weight. Data to left of the solid vertical lines are from the last ovarian cycle before OVX (x-axis labels appear in panel B: Preovx; D1, diestrus 1, D2 diestrus 2; P, proestrus; E, estrus), and data to the right of the solid vertical lines are sham-operated intact rats (solid circles), OVX rats treated with EB (triangles), and OVX rats treated with the oil vehicle (open circles); dashed vertical lines divide the numbered 4-day treatment cycles (days 1–4), which are aligned so that the last day of each cycle is the second day after EB injection, the day that models estrus. B: OVX increased and cyclic estradiol treatment normalized daily food intake (x-axis labels explained above). Note 1) that OVX elevated, and EB normalized, the basal level of daily food intake (tonic estrogenic inhibition of eating; tested on day 2) and 2) that OVX eliminated, and EB reinstated, the drop in food intake during estrus in intact rats and on cycle day 4 in OVX rats (phasic or cyclic estrogenic inhibition of eating). C: OVX increased and cyclic estradiol treatment normalized nocturnal spontaneous meal size. Triangles indicate mean meal sizes during the last cycle Preovx (abbreviations as above); solid circles indicate mean Postovx meal sizes during cycles 2–7 of cyclic EB treatment (injection time indicated by arrow); and open circles indicate mean Postovx meal sizes in control rats treated with the oil vehicle. +Significantly different from intact rats and EB-treated rats on day 2; *Significantly different from diestrus 2 (intact group) or day 2 (OVX group). Meal frequency was not increased by OVX or decreased by EB (data not shown). Reprinted from Hormones and Behavior, Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats, 42: 461–471, 2002; republished with permission from Elsevier; from Asarian and Geary (15).