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Antipsychotic drug-induced weight gain: development of an animal model

Abstract

OBJECTIVE:

Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition.

METHODS:

Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment.

RESULTS:

After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased.

CONCLUSIONS:

Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

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References

  1. Bridler R, Umbricht D . Atypical antipsychotics in the treatment of schizophrenia. Swiss Med Wkly 2003; 133: 63–76.

    CAS  PubMed  Google Scholar 

  2. Arato M, O’Connor R, Meltzer HY . A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. Int Clin Psychopharmacol 2002; 17: 207–215.

    Article  CAS  PubMed  Google Scholar 

  3. Volavka J, Czobor P, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Cooper TB, Chakos M, Lieberman JA . Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry 2002; 159: 255–262.

    Article  PubMed  Google Scholar 

  4. Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA . Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism. J Pharmacol Exp Ther 2000; 293: 8–14.

    CAS  PubMed  Google Scholar 

  5. Weiden PJ, Mackell JA, McDonnell DD . Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res 2004; 66: 51–57.

    Article  PubMed  Google Scholar 

  6. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ . Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–1696.

    CAS  PubMed  Google Scholar 

  7. Jones B, Basson BR, Walker DJ, Crawford AM, Kinon BJ . Weight change and atypical antipsychotic treatment in patients with schizophrenia. J Clin Psychiatry 2001; 62 (Suppl 2): 41–44.

    CAS  PubMed  Google Scholar 

  8. Baptista T . Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand 1999; 100: 3–16.

    Article  CAS  PubMed  Google Scholar 

  9. Allison DB, Casey DE . Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 2001; 62 (Suppl 7): 22–31.

    CAS  PubMed  Google Scholar 

  10. Russell JM, Mackell JA . Bodyweight gain associated with atypical antipsychotics: epidemiology and therapeutic implications. CNS Drugs 2001; 15: 537–551.

    Article  CAS  PubMed  Google Scholar 

  11. Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, Allison DB . Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 2001; 101: 277–288.

    Article  CAS  PubMed  Google Scholar 

  12. Benvenga MJ, Leander JD . Increased food consumption by clozapine, but not by olanzapine, in satiated rats. Drug Dev Res 1997; 41: 48–50.

    Article  CAS  Google Scholar 

  13. Lee MD, Clifton PG . Meal patterns of free feeding rats treated with clozapine, olanzapine, or haloperidol. Pharmacol Biochem Behav 2002; 71: 147–154.

    Article  CAS  PubMed  Google Scholar 

  14. Hartfield AW, Moore NA, Clifton PG . Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat. Psychopharmacology (Berl) 2003; 167: 115–122.

    Article  CAS  Google Scholar 

  15. Kaur G, Kulkarni SK . Studies on modulation of feeding behavior by atypical antipsychotics in female mice. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 277–285.

    Article  CAS  PubMed  Google Scholar 

  16. Baptista T, Parada M, Hernandez L . Long term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved? Pharmacol Biochem Behav 1987; 27: 399–405.

    Article  CAS  PubMed  Google Scholar 

  17. Baptista T, Hernandez L, Hoebel BG . Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus. Pharmacol Biochem Behav 1990; 37: 227–229.

    Article  CAS  PubMed  Google Scholar 

  18. Baptista T, Contreras Q, Teneud L, Albornoz MA, Acosta A, Paez X, de Quijada M, Lacruz A, Hernandez L . Mechanism of the neuroleptic-induced obesity in female rats. Prog Neuropsychopharmacol Biol Psychiatry 1998; 22: 187–198.

    Article  CAS  PubMed  Google Scholar 

  19. Baptista T, Araujo dB, Ying Kin NM, Beaulieu S, Walker D, Joober R, Lalonde J, Richard D . Comparative effects of the antipsychotics sulpiride or risperidone in rats. I: bodyweight, food intake, body composition, hormones and glucose tolerance. Brain Res 2002; 957: 144–151.

    Article  CAS  PubMed  Google Scholar 

  20. Baptista T, Lacruz A, Paez X, Hernandez L, Beaulieu S . The antipsychotic drug sulpiride does not affect bodyweight in male rats. Is insulin resistance involved? Eur J Pharmacol 2002; 447: 91–98.

    Article  CAS  PubMed  Google Scholar 

  21. Pouzet B, Mow T, Kreilgaard M, Velschow S . Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human. Pharmacol Biochem Behav 2003; 75: 133–140.

    Article  CAS  PubMed  Google Scholar 

  22. Ota M, Mori K, Nakashima A, Kaneko YS, Fujiwara K, Itoh M, Nagasaka A, Ota A . Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats. Clin Exp Pharmacol Physiol 2002; 29: 980–989.

    Article  CAS  PubMed  Google Scholar 

  23. Goudie AJ, Smith JA, Halford JC . Characterization of olanzapine-induced weight gain in rats. J Psychopharmacol 2002; 16: 291–296.

    Article  CAS  PubMed  Google Scholar 

  24. Raggi MA, Casamenti G, Mandrioli R, Izzo G, Kenndler E . Quantitation of olanzapine in tablets by HPLC, CZE, derivative spectrometry and linear voltammetry. J Pharm Biomed Anal 2000; 23: 973–981.

    Article  CAS  PubMed  Google Scholar 

  25. Nagy TR, Clair AL . Precision and accuracy of dual-energy X-ray absorptiometry for determining in vivo body composition of mice. Obes Res 2000; 8: 392–398.

    Article  CAS  PubMed  Google Scholar 

  26. Dobush GR, Ankey CD, Krementz DG . The effect of apparatus, extraction time, and solvent type on lipid extractions of snow geese. Can J Zool 1985; 63: 1917–1920.

    Article  CAS  Google Scholar 

  27. Toothaker LE . Multiple Comparisons for Researchers. Sage Publications: Newbury Park; 1991.

    Google Scholar 

  28. Gothelf D, Falk B, Singer P, Kairi M, Phillip M, Zigel L, Poraz I, Frishman S, Constantini N, Zalsman G, Weizman A, Apter A . Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine. Am J Psychiatry 2002; 159: 1055–1057.

    Article  PubMed  Google Scholar 

  29. Martin A, Koenig K, Scahill L, Bregman J . Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999; 9: 99–107.

    Article  CAS  PubMed  Google Scholar 

  30. Theisen FM, Linden A, Konig IR, Martin M, Remschmidt H, Hebebrand J . Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine. J Neural Transm 2003; 110: 111–121.

    CAS  PubMed  Google Scholar 

  31. Eder U, Mangweth B, Ebenbichler C, Weiss E, Hofer A, Hummer M, Kemmler G, Lechleitner M, Fleischhacker WW . Association of olanzapine-induced weight gain with an increase in body fat. Am J Psychiatry 2001; 158: 1719–1722.

    Article  CAS  PubMed  Google Scholar 

  32. David SR, Taylor CC, Kinon BJ, Breier A . The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000; 22: 1085–1096.

    Article  CAS  PubMed  Google Scholar 

  33. Cohen S, Fitzgerald B, Okos A, Khan S, Khan A . Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation. J Clin Psychiatry 2003; 64: 60–62.

    Article  CAS  PubMed  Google Scholar 

  34. Nasrallah H . A review of the effect of atypical antipsychotics on weight. Psychoneuroendocrinology 2003; 28 (Suppl 1): 83–96.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported in part by NIH grant P30DK56336, DK68261 grants from the NARSAD Foundation and Eli Lilly & Co., and the Veteran Affairs Medical Research Program. We thank Dr Steve Barnes, Dr Donald Muccio, Ms Grace Walton, and Dr Benjamin Davis for their contributions to the manuscript. We received technical assistance from Pfizer Pharmaceutical.

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Correspondence to D B Allison.

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Cope, M., Nagy, T., Fernández, J. et al. Antipsychotic drug-induced weight gain: development of an animal model. Int J Obes 29, 607–614 (2005). https://doi.org/10.1038/sj.ijo.0802928

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