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Effects of sub-chronic antipsychotic drug treatment on body weight and reproductive function in juvenile female rats

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Abstract

Rationale

Weight gain caused by some antipsychotics is not only confined to adults but can also adversely affect both children and adolescents. Indeed, olanzapine and risperidone have been associated with extreme weight gain in adolescents even greater than that reported in adults. We have recently shown substantial weight gain in adult female rats following treatment with olanzapine and risperidone but not ziprasidone.

Objectives

The aim of the present study was to compare the effects of several antipsychotics on weight gain and reproductive function in juvenile (aged 7 weeks) female hooded Lister rats.

Methods

Olanzapine (4 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), sulpiride (10 mg/kg), haloperidol (0.5 mg/kg) or vehicle was administered i.p. once per day for 21 days. Body weight, food and water intake were measured daily, in addition to the determination of stage of the oestrous cycle.

Results

Sub-chronic administration of olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone, significantly increased body weight compared to vehicle-treated animals during weeks 1–3. Sulpiride significantly increased food and water intake. Significantly increased percentage intra-abdominal fat weight was observed in olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone-treated animals. Marked disruption of the oestrous cycle was observed in all but the ziprasidone-treated group, which continued to have regular 4-day oestrous cycles.

Conclusions

Weight gain observed in these juvenile animals was 1.5–2 times greater than that previously observed in adult rats. These findings have important implications for the use of antipsychotics in children and adolescent patients.

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Acknowledgements

The authors would like to thank GSK for the generous supply of ziprasidone and olanzapine.

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Authors and Affiliations

  1. Bradford School of Pharmacy, The University of Bradford, Bradford, BD7 1DP, UK

    M. J. Fell, J. C. Neill, C. Rao & K. M. Marshall

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  1. M. J. Fell
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  2. J. C. Neill
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  3. C. Rao
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  4. K. M. Marshall
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Correspondence to J. C. Neill.

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Fell, M.J., Neill, J.C., Rao, C. et al. Effects of sub-chronic antipsychotic drug treatment on body weight and reproductive function in juvenile female rats. Psychopharmacology 182, 499–507 (2005). https://doi.org/10.1007/s00213-005-0131-3

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  • DOI: https://doi.org/10.1007/s00213-005-0131-3

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