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

Molecular Psychiatry volume 5, pages 70–76 (2000)Cite this article

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). SUL-treated 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.

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References

  1. Bhavnani SM, Levin GM . Antipsychotic agents: a survey of the prevalence, severity and burden of side effects Int Clin Psychopharmacol 1996; 11: 1–12

    Article  CAS  Google Scholar 

  2. Høyberg OJ, Fensbo C, Remvig J, Linjaerde O, Sloth-Nielsen M, Salvesen Y . Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations Acta Psychiatr Scand 1993; 88: 395–402

    Article  Google Scholar 

  3. Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M . Clozapine-induced weight gain: prevalence and clinical relevance Am J Psychiat 1992; 149: 68–72

    Article  CAS  Google Scholar 

  4. Olanzapine . Lilly Lab 1996 Monograph October: 71–72

  5. Silverstone T, Smith G, Goodall E . Prevalence of obesity in patients receiving depot antipsychotics Br J Pschiat 1988; 153: 214–217

    Article  CAS  Google Scholar 

  6. Baptista T, Parada MA, Hernández 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  Google Scholar 

  7. Baptista T, Parada MA, Murzi E . Puberty modifies sulpiride effects on body weight in rats Neurosci Lett 1988; 92: 161–164

    Article  CAS  Google Scholar 

  8. Baptista T, Hernández L, Hoebel BG . Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus Pharmacol Biochem Behav 1990; 37: 533–537

    Article  Google Scholar 

  9. Baptista T, Murzi E, Hernández L, Burguera JL, de Burguera M . Mechanism of the sex-dependent effect of lithium on body weight in rats Pharmacol Biochem Behav 1991; 38: 533–537

    Article  CAS  Google Scholar 

  10. Baptista T, Teneud L, Hernández L . Enhancement of amphetamine anorexia after chronic administration of sulpride in rats Pharmacol Biochem Behav 1993; 45: 45–49

    Article  CAS  Google Scholar 

  11. Baptista T, López MA, Teneud L, Contreras Q, Alastre T, Quijada M et al. Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates Pharmacopsychiatry 1997; 30: 35–43

    Google Scholar 

  12. Baptista T, Araujo de Baptista E, Altemus M, Weiss SRB, Hernández L . Tamoxifen prevents sulpiride-induced obesity in rats Pharmacol Biochem Behav 1997; 57: 215–222

    Article  CAS  Google Scholar 

  13. Baptista T, Albornoz MA, Teneud L, Contreras Q, Páez X, LaCruz A et al. Mechanism of the neuroleptic-induced obesity in female rats Prog Neuro-Psychopharmacol & Biol Psychiat 1998; 22: 187–198

    Article  CAS  Google Scholar 

  14. Baptista T, LaCruz A, Hernández L . Glucose tolerance and serum insulin levels in an animal model of obesity induced by the antipsychotic drug sulpiride Pharmacol & Toxicol 1998; 83: 57–61

    Article  CAS  Google Scholar 

  15. Baptista T, Alvarez L, LaCruz A, de Mendoza S, Hernández L . Glucose tolerance and serum insulin levels in an animal model of obesity induced by subacute or chronic administration of antipsychotic drugs Prog Neuro-Psychopharmacol & Biol Psychiat 1999; 23: 277–287

    Article  CAS  Google Scholar 

  16. Parada MA, Hernández L, Páez X, Baptista T, Puig de Parada M, Quijada M . Mechanism of the sulpiride-induced obesity in rats Pharmacol Biochem Behav 1989; 33: 45–50

    Article  CAS  Google Scholar 

  17. Shimizu H, Shimomura Y, Urhara Y, Kobayashi Y, Kobayashi Y, Kobayashi S . Involvement of sex hormone in body weight gain by selective D2 receptor antagonist sulpiride Exp Clin Endocrinol 1990; 96: 25–29

    Article  CAS  Google Scholar 

  18. Wagssstaff AJ, Fitton A, Benfield P . Sulpiride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in schizophrenia CNS Drugs 1994; 2: 313–333

    Article  Google Scholar 

  19. Campfield LA, Smith FJ, Burn P . The OB Protein (leptin)—a link between adipose tissue mass and central neural networks Horm Metab Res 1996; 12: 619–632

    Article  Google Scholar 

  20. Friedman JM, Halaas JL . Leptin and the regulation of body weight in mammals Nature 1998; 22: 763–770

    Article  Google Scholar 

  21. Remesar X, Rafecas I, Fernández-López JA, Alemany M . Leptin Medic Res Rev 1997; 17: 225–234

    Article  CAS  Google Scholar 

  22. Woods SC, Seeley RJ, Porte D, Schwartz MW . Signals that regulate food intake and energy homeostasis Science 1998; 280: 1378–1382

    Article  CAS  Google Scholar 

  23. Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B et al. Transient increase in obese gene expression after food intake or insulin administration Nature 1995; 377: 527–529

    Article  CAS  Google Scholar 

  24. Yoshida T, Hayashi M, Monkawa T, Saruta T . Regulation of obese gene expression by hormonal factors in primary cultures of rats adipocytes Eur J Endocrinol 1996; 135: 619–625

    Article  CAS  Google Scholar 

  25. Larrson H, Elmstahl S, Ahren B . Plasma leptin levels correlate to islet function independently of body fat in postmenopausal women Diabetes 1996; 45: 1580–1584

    Article  Google Scholar 

  26. Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL et al. Leptin is a metabolic signal to the reproductive system Endocrinol 1996; 137: 3144–3147

    Article  CAS  Google Scholar 

  27. Chehab FF, Mounzih K, Lu R, Lim ME . Early onset of reproductive function in normal female mice treated with leptin Science 1997; 275: 88–90

    Article  CAS  Google Scholar 

  28. Mantzoros CS, Flier JS, Rogol AD . A longitudinal assessment of hormonal and physical alternations during normal puberty in boys. Rising leptin levels may signal the onset of puberty J Clin Endocrinol Metab 1997; 82: 1066–1070

    CAS  Google Scholar 

  29. Bromel T, Blum WF, Zeigler A, Schulz E, Bender M, Fleischhaker C et al. Serum leptin levels increase rapidily after initiation of clozapine therapy Mol Psychiatry 1998; 3: 76–80

    Article  CAS  Google Scholar 

  30. Kraus T, Haack M, Schuld A, Hinze-Selch D, Kuhn M, Uhr M et al. Body weight and leptin plasma levels during treatment with antipsychotic drugs Am J Psychiatry 1999; 2: 312–314

    Google Scholar 

  31. ILAR Committee on Care and Use of Laboratory Animals . Guide for the Care and Use of Laboratory Animals. NIH Pub. No. 86–23 US Department of Health and Human Services: Washington DC 1985

  32. Mueller WM, Gregoire FC, Stanhope KL, Mobbs CV, Mizuno TM, Warden CH et al. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes Endocrinology 1998; 139: 551–558

    Article  CAS  Google Scholar 

  33. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L . A nutrient-sensing pathway regulates leptin gene expression in muscle and fat Nature 1998; 393: 684–688

    Article  CAS  Google Scholar 

  34. Baptista T, Molina MG, Martinez JL, Quijada M, Calanche I, Acosta A et al. Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy premenopausal women: relationship with body weight regulation Pharmacopsychiatry 1997; 30: 256–262

    Article  CAS  Google Scholar 

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Acknowledgements

This paper was supported by CONICIT Grants S196000775, and 97003895024.

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Authors and Affiliations

  1. Laboratory of Behavioral Physiology, School of Medicine, University of Los Andes, Mérida, Venezuela

    A Lacruz, T Baptista & L Hernández

  2. Metabolism Center, Mérida, Venezuela

    S de Mendoza & J M Mendoza-Guillén

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  1. A Lacruz
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  2. T Baptista
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  3. S de Mendoza
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  5. L Hernández
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Correspondence to T Baptista.

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Lacruz, A., Baptista, T., de Mendoza, S. et al. Antipsychotic drug-induced obesity in rats: correlation between leptin, insulin and body weight during sulpiride treatment. Mol Psychiatry 5, 70–76 (2000). https://doi.org/10.1038/sj.mp.4000566

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