The antipsychotic drug sulpiride does not affect bodyweight in male rats. Is insulin resistance involved?

Baptista, Trino; Lacruz, Anny; Páez, Ximena; Hernández, Luis; Beaulieu, Serge

doi:10.1016/s0014-2999(02)01816-2

Cited by 49 publications

(38 citation statements)

References 43 publications

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“…Weight gain and hyperphagia were found in female rats treated with sulpiride [16][17][18] and risperidone, 19 but not in male rats treated with sulpiride, 20 risperidone, 19 or olanzapine. 21 Subcutaneous injections of risperidone for 21 days increased the food intake (12% fat in diet) and rate of BW gain in 8-weekold male Sprague-Dawley rats.…”

Section: Introductionmentioning

confidence: 89%

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

et al. 2005

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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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Section: Introductionmentioning

confidence: 89%

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

et al. 2005

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“…Others have reported a slight or non-significant increase in serum insulin levels following chronic haloperidol administration to male rats (Manzanares et al, 1988 andMinet-Ringuet et al, 2005). This increase in circulating insulin has been suggested as one of the reasons preventing body weight gain in male rats treated with haloperidol (Baptista et al, 2002c), which follows Eckel's proposal that insulin resistance may be an adaptive response for weight maintenance (Eckel, 1992). While hyperinsulinemia, insulin resistance and dyslipidemia are often detected in people treated with antipsychotics (Clark andBurge, 2003 andSacchetti et al, 2005), it is unclear whether these conditions are direct drug effects or are related to weight gain since many of these subjects have gained significant weight through the course of antipsychotic drug treatment.…”

Section: Effect Of Haloperidol or Risperidone On Body Tissue Compositionmentioning

confidence: 98%

“…Indeed, chronic administration of sulpiride, a dopamine D2-D3 receptor antagonist, leads to elevated circulating insulin and glucose levels in rats during a glucose tolerance test (Baptista et al, 2002c). In addition, dopamine D2-like receptors are expressed in both rat and human pancreatic β cells and mediate inhibition of glucose-stimulated but not basal insulin secretion (Rubi et al, 2005).…”

Section: Effect Of Haloperidol or Risperidone On Body Tissue Compositionmentioning

confidence: 99%

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

et al. 2006

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Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28 days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), orgonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.

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“…In rodents, L -DOPA injection results in the accumulation of dopamine in pancreatic β cells and an inhibitory action on insulin response to different secretagogues [60,61], whilst in male rats treated with a dopamine antagonist, high glucose and insulin levels were observed [62]. Insulin secretion is primarily controlled by metabolism-secretion coupling, and is mainly regulated by glucose, but this process can be modulated by the central nervous system through parasympathetic and sympathetic nerves [63].…”

Section: D2rs and Glucose Metabolismmentioning

confidence: 99%

New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the <i>Drd2</i><sup>–/–</sup> Mouse

García-Tornadú

Millán²,

Recouvreux³

et al. 2010

Neuroendocrinology

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Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2^–/–) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2^–/– mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2^–/– mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2^–/– mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival.

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The antipsychotic drug sulpiride does not affect bodyweight in male rats. Is insulin resistance involved?

Cited by 49 publications

References 43 publications

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

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

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the <i>Drd2</i><sup>–/–</sup> Mouse

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