Dexfenfluramine: action with estradiol on food intake and body weight in ovariectomized rats

Previous work from this laboratory has shown that chronic administration of dexfenfluramine (DF) caused substantial weight loss in rats that were overweight 3-4 mo after ovariectomy (OVX), but not in OVX rats that were of normal weight, as a result of estrogen replacement. The present study was conducted to determine whether the enhanced weight loss in the former group is because of either overweight per se or an inhibitory effect of estrogen on DF. Starting either 0, 6, or 14 wk after OVX, when weight gain was zero, moderate, or near maximal, respectively, rats received a 12-day regimen of either estradiol or the oil vehicle and either DF (3 mg.kg-1.day-1 by osmotic minipump) or no drug. DF had no effect on either food intake or weight gain of groups treated during 0-2 wk after OVX but had significant anorectic and weight loss actions in groups treated 6-8 and 14-16 wk after OVX. Estrogen had a similar effect at all three times and in the 14-wk group produced an effect that was additive with that of DF. Measures of plasma glucose and triglycerides and adipose tissue lipoprotein lipase activity did not correlate with the effectiveness of the drug to promote weight loss.