Antipsychotic drug therapy most notably with atypical agents such as clozapine and olanzapine, often results in considerable body weight gain, which may have detrimental effects on patient compliance, morbidity and mortality (Allison et al ., 1999). Previous studies in our laboratory have shown that olanzapine (4mg/kg^-1) significantly increased body weight, food intake and intra-abdominal fat deposition in juvenile and adult female hooded-Lister rats (Fell et al., 2004). The present study examined the effects of oestrogen deficiency on olanzapine induced body weight gain and hyperphagia in female rats.

Subjects were 12 adult female hooded-Lister rats, group housed under standard laboratory conditions. Under halothane anesthesia, rats were ovariectomised via translumbar incisions. Five weeks after surgery, rats were divided into two groups consisting of six rats per group. Olanzapine (4mg/kg^-1) or vehicle (saline) was administered once per day for 21 days via a single daily i.p. injection. Body weight, and food and water intakes were measured daily. On day 22, animals were sacrificed, intra-abdominal fat and wet and dry uterine weights recorded. Statistical comparisons were made using the Students t-test. Data are expressed as mean ± SEM (n=6 per group and per cage).

Sub-chronic administration of olanzapine induced a significant weight loss throughout the 3-week study (see table 1) compared to vehicle treated animals (p<0.001). No effects of olanzapine were seen on food or water intake. Furthermore, no effects of olanzapine were observed on intra-abdominal fat deposition or wet and dry uterine weights.

Table 1.Effect of olanzapine 4mg/kg^-1 on mean body weight change in ovariectomised rats over a three week period (***p<0.001 significant difference from the vehicle group at that time point)

Bilateral ovariectomy completely abolished weight gain and hyperphagia previously demonstrated in female rats following olanzapine administration. The present study suggests therefore, that estrogen is involved in olanzapine induced weight gain and hyperphagia in female rats.

Allison, D.B et al (1999) Am . J. Psychiatry. 156, 1686-1696.
Fell, M.J et al (2004) J . Psychopharm. 18,149-155.