Mechanism of the body weight increase induced by systemic sulpiride

Long-term intraperitoneal administration of sulpiride induced body weight increase in female but not in male rats. The hypothesis that systemic sulpiride causes an endocrine unbalance which in turn causes body weight gain and hyperphagia was tested in four experiments. First, it was shown that even when they are on a high-fat diet male rats do not show body weight gain induced by systemic sulpiride. Second, sulpiride suppressed the estrous cycle. Third, gonadectomy prevented the body weight gain induced by systemic sulpiride in female rats. Fourth, estradiol simultaneously administered with sulpiride prevented the expected sulpiride-induced body weight gain. These results are discussed in terms of an hypothetical functional castration produced by systemic sulpiride. The well known hyperprolactinemia, induced by the pituitary D2 dopamine receptor blockade, might bring about an impairment of the steroidogenesis with subsequent decrease in estrogens level, which in turn might be responsible for the hyperphagia and body weight increase induced by systemic injections of sulpiride.