There is considerable evidence that weight gain is a serious side effect of some antipsychotic drugs. Previously, we have observed substantial weight gain in female rats treated sub-chronically with olanzapine and risperidone. The effect of risperidone on weight gain was produced with markedly impaired reproductive function in contrast to olanzapine which induced weight gain, but had no effect on reproductive function (Fell et al, 2004 a & b). The aim of the present study was to investigate the effect of the novel antipsychotic ziprasidone on body weight gain and reproductive function in female hooded-Lister rats.

Subjects were 18 adult female hooded-Lister rats (203 ± 3g) group housed under standard laboratory conditions. Ziprasidone (1-2.5 mg/kg i.p) or vehicle was administered once per day for 28 days and body weight, food and water intake measured, in addition to histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 22, the rats were sacrificed and the uterine weight recorded, intra-abdominal fat weight and plasma prolactin levels were also measured. Statistical comparisons were made using 2 way and 1 way ANOVA with post hoc Dunnett's t-test. Data are expressed as mean ± SEM (n=6 per group and per cage). Oestrous cycle data were analysed using Fisher's exact test.

Administration of ziprasidone failed to induce significant weight gain in female rats during weeks 1- 3, however, significant weight gain was observed during week 4 at 2.5mg/kg, (table 1). Ziprasidone had no effect on food intake at any time point. A small but significant reduction in water intake (115.1 ± 2.1g vehicle group compared to 104.6 ± 2.2g ziprasidone group, p<0.05) was observed during the first week of treatment at 2.5 mg/kg ziprasidone. Ziprasidone had no effect on intra-abdominal fat weight, dry uterine weight or plasma prolactin levels. Furthermore all ziprasidone treated animals displayed a normal four day oestrous cycle.

Table 1. Effect of ziprasidone 1-2.5 mg/kg on percentage weight gain over a four week period (p<0.05 significant difference from the vehicle group)

These results showing no weight gain in week 1 are in agreement with those of Daniels et al., (2003) and are the first to show that ziprasidone is without effect on reproductive function in the rat.

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Daniels A.J et al (2003) J.Psychpharm 17 (3), A52.
Fell M.J et al (2004a) Eur Neuropsychopharm: in press.
Fell M.J et al (2004b) J.Psychopharm 18 (2): 149-155.