Antipsychotic drug-induced obesity in rats: correlation between leptin, insulin and body weight during sulpiride treatment

Abstract

Sulpiride (SUL, 20 mg kg −1 day −1 ) induces weight gain, hyperphagia, hyperprolactinemia, hypogonadism, and perhaps increased insulin sensitivity in rats. Leptin seems to signal the brain about the size of body fat stores and nutrient metabolism. We evaluated the basal serum leptin levels in rats after acute (1 h) or prolonged SUL or vehicle administration (10, 20 and 30 days). At days 10 and 30 leptin was also assessed during a glucose overload test. As the maximal weight gain during SUL administration is observed at days 10-15 of treatment, leptin was measured in a comparison group of insulin-treated rats (5 IU day −1 for 10 days). SULtreated rats significantly gained weight. However, leptin levels were not significantly increased at any time-point of treatment. SUL did not affect insulin levels either. By contrast, leptin levels were significantly elevated after insulin administration, along with weight gain and hyperinsulinemia. An opposite correlation was also observed at day 10: leptin and insulin correlated negatively in the SUL group and positively in the insulin group. In addition, leptin and the magnitude of weight gain tended to correlate positively after SUL treatment, but negatively after insulin administration. SUL-treated rats, thus, appear to exhibit an unusual type of weight gain, characterized by normal circulating leptin and insulin levels. Such a particular leptin profile may be related to hyperprolactinemia, hypogonadism or lack of hyperinsulinemia. Molecular Psychiatry (2000) 5, 70-76.

Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats

“…In our experiments, we used female subjects in accord with wellaccepted opinion on this model (Lacruz et al 2000;Goudie et al 2002;Pouzet et al 2003;Arjona et al 2004;Fell et al 2004aFell et al ,b, 2005. Several previous reports confirmed that the weight gain-inducing effects of antipsychotic drugs such as sulpiride, olanzapine and haloperidol are present in female, but not in male rats (Baptista et al 2002;Pouzet et al 2003).…”

“…In a proposed animal model of antipsychotic drug-induced weight gain, chronic administration of olanzapine (Goudie et al 2002;Pouzet et al 2003;Fell et al 2004a,b;Arjona et al 2004), sulpiride (Baptista et al 1998a(Baptista et al ,b, 2002Lacruz et al 2000) or risperidone (Baptista et al 2002;Fell et al 2004a) induced weight gain in female rats, mimicking their effect on body weight in the clinic (Baptista 1999;Gothelf et al 2002;Bobes et al 2003). In order to investigate how closely proposed model mimics the clinical picture, it needs to be determined whether antipsychotic drug-induced weight gain in rats shares characteristics and is mediated by mechanisms similar to those observed in human patients.…”

Identification of drug‐induced hyper‐ or hypoprolactinemia in the female rat based on general and reproductive toxicity study parameters

“…As a consequence, ovarian weights are increased and hypertrophic CL can be noted grossly and/or microscopically (Yuan and Foley, 2002). However, prolactin can also have antigonadotrophic effects as seen during lactation, following pituitary transplants, or administration of high-dose dopamine antagonists causing markedly increased prolactin concentrations, decreased ovarian weights, and an extended anovulatory period (Smith, 1980;Baptista et al, 2000;Lacruz et al, 2000;Moro et al, 2001). …”

The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats

“…It appears that, in spite of developing significant increases in body weight and adiposity, antipsychotic drug-treated rats consistently display low/normal glucose levels, normal insulin levels, and normal blood lipid and leptin levels (Baptista et al 1999(Baptista et al , 2002aLacruz et al 2000). The failure to reproduce the adverse effects of antipsychotic drugs on glucose regulation and lipid profile akin to that seen in antipsychotic-treated patients is an important limitation of studies of antipsychotic drug effects in rats.…”