TAMOXIFEN PREVENTS SULPIRIDE-INDUCED WEIGHT-GAIN IN FEMALE RATS

To evaluate its potential utility in counteracting neuroleptic-induced obesity, the effects of long-term administration of tamoxifen (TAM) o n body weight (BW) and food intake (FI) of gonadalIy intact and sulpir ide-treated (SUL) female rats were assessed. In addition, estradiol an d prolactin serum levels were measured in rats treated with SUL, SUL p lus TAM and SUL plus bromocriptine (BR). TAM, at doses of 10, 50 and 1 00 pg, significantly decreased BW gain; FI was significantly reduced a t the doses of 50 and 100 mu g. In addition, doses of TAM ranging from 5-100 mu g completely prevented SUL-induced BW gain and hyperphagia. BR also prevented SUL effects on BW and FI. In contrast to BR, concomi tant administration of TAM did not prevent SUL-induced hyperprolactine mia. Estradiol levels were not modified by SUL alone or SUL plus BR, b ut they were significantly increased in the animals treated with TAM p lus SUL. Neuroleptic-induced obesity in female rats might be related t o an alteration in gonadal steroid balance secondary to hyperprolactin emia. While BR might counteract neuroleptic-induced weight gain by pre venting hyperprolactinemia, TAM might directly interact with estrogen receptors, or indirectly increase estradiol levels. The use of TAM in preventing neuroleptic-induced obesity in humans warrants further inve stigation. (C) 1997 Elsevier Science Inc.