Abstract
Research studies have shown that chronic administration of some antipsychotic drugs induces obesity in female but not in male. To explore the mechanisms involved in this effect, we administrated the dopamine antagonist sulpiride (40 mg/kg) or vehicle intraperitoneally to adult male mice during 45 days and then the glucose tolerance and serum levels of insulin, serum, and testicular testosterone and prolactin, and blood estrogen levels were evaluated. Chronic sulpiride administration did not affect body weight. However, prolactin levels and the area under the glucose and insulin curves were significantly elevated. Sulpiride significantly decreased testosterone and increased estrogen levels (p < 0.05). After prolonged administration, sulpiride did not affect body weight, so this lack of effect may be related to the impairment of insulin sensitivity which prevents body weight gain and deals with other effects of sulpiride that cause adiposity promotion such as hyperprolactinemia. Future studies must evaluate other neurotransmitters involved in food intake regulation such as histamine and serotonin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baptista T, Parada M, Hernandez L (1987) Long term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved? Pharmacol Biochem Behav 27(3):399–405
Baptista T, Lacruz A, Pàez X, Hernàndez L, Beaulieu S (2002) The antipsychotic drug sulpiride does not affect bodyweight in male rats. Is insulin resistance involved? Eur J Pharmacol 447(1):91–98
Dewan ZF, Morris ID, Lendon RG (2000) Administration of exogenous testosterone in the adult rat and its effects on reproductive organs, sex hormones and body-weight. Bangladesh Med Res Counc Bull 26(2):48–55
Eckel RH (1992) Insulin resistance: an adaptation for weight maintenance. Lancet 340:1452–1453
Fric M, Laux G (2003) Plasma prolactin level and incidence of adverse endocrinologic effects during therapy with atypical neuroleptics. Psychiatr Prax 30(2):S97–S101
Greenman Y, Tordjman K, Stern N (1998) Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol 48(5):547–553
Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106(4):473–481
Kalla NR, Nisula BC, Menard R, Loriaux DL (1980) The effect of estradiol on testicular testosterone biosynthesis. Endocrinology 106(1):35–39
Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M (1999) Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol 19(1):57–61
López MM, Navarro JF (1996) Effect of sulpiride on body weight after chronic administration in male mice. Psicothema 8(3):609–612
Luboshitzky R, Kaplan-Zverling M, Shen-Orr Z, Nave R, Herer P (2002) Seminal plasma androgen/oestrogen balance in infertile men. Int J Androl 25(6):345–351
Matsuda M, Mori T (1996) Effect of estrogen on hyperprolactinemia-induced glucose intolerance in SHN mice. Proc Soc Exp Biol Med 212:243–247
McKeage K, Plosker GL (2004) Amisulpride: a review of its use in the management of schizophrenia. CNS Drugs 18(13):933–956
McMurdo ME, Howie PW, Lewis M, Marnie M, McEwen J, McNeilly AS (1987) Prolactin response to low dose sulpiride. Br J Clin Pharmacol 24(2):133–137
Parada MA, Hernandez L, Paez X, Baptista T, Puigde de Parada M, De Quijada M (1989) Mechanism of the body weight increase induced by systemic sulpiride. Pharmacol Biochem Behav 33(1):45–50
Ravussin E, Bouchard C (2000) Human genomics and obesity: finding appropriate drug targets. Eur J Pharmacol 410(2–3):131–145
Redolat R, Brain PF, Simón VM (1991) Sulpiride has an anti aggressive effect in mice without markedly depressing motor activity. Neuropharmacology 30:41–46
Shimizu H, Shimomura Y, Urhara Y, Kobayashi Y, Kobayashi S (1990) Involvement of sex hormone in body weight gain by selective D2 antagonist sulpiride. Exp Clin Endocrinol 96(1):25–29
Torre DL, Falorni A (2007) Pharmacological causes of hyperprolactinemia. Ther Clin Risk Manag 3(5):929–951
Von Bahr C, Wiesel FA, Movin G, Eneroth P, Jansson P, Nilsson L, Ogenstad S (1991) Neuroendocrine responses to single oral doses of remoxipride and sulpiride in healthy female and male volunteers. Psychopharmacology (Berl) 103(4):443–448
Wagstaff JA, Fitton A, Benfield P (1994) Sulpiride: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in schizophrenia. CNS Drugs 2(4):313–333
Wetzel H, Wiesner J, Hiemke C, Benkert O (1994) Acute antagonism of dopamine D2-like receptors by amisulpride: effects on hormone secretion in healthy volunteers. J Psychiatr Res 28(5):461–473
Zhang Q, Bai Q, Yuan Y, Liu P, Qiao J (2010) Assessment of seminal estradiol and testosterone levels as predictors of human spermatogenesis. J Androl 31(2):215–220
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ahmadi, A., Ahmadi, E. The antipsychotic drug sulpiride induces insulin intolerance but does not affect body weight in adult male mice. Comp Clin Pathol 25, 53–58 (2016). https://doi.org/10.1007/s00580-015-2138-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-015-2138-4