Risperidone alters food intake, core body temperature, and locomotor activity in mice.

Risperidone alters food intake, core body temperature, and locomotor activity in mice.
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DOI:
10.1016/j.physbeh.2008.11.011
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发表时间:
2009-03-02
影响因子:
2.9
通讯作者:
Nagy, Tim R.
Nagy, Tim R.
中科院分区:
医学3区
文献类型:
--
作者:
Cope, Mark B.;Li, Xingsheng;Jumbo-Lucioni, Patricia;DiCostanzo, Catherine A.;Jamison, Wendi G.;Kesterson, Robert A.;Allison, David B.;Nagy, Tim R.

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利培酮在雌性小鼠中诱导显著的体重增加;然而,与该效应相关的潜在机制尚不清楚。我们研究了利培酮对自发活动,核心体温,解偶联蛋白(UCP)和下丘脑食欲素mRNA表达的影响。使雌性C57 BL/6 J小鼠适应单独圈养,并随机分配至利培酮(4 mg/kg BW* 天)或安慰剂(PLA)组。在48小时内测量活动和体温,每周两次,持续3周。每周测量摄食量和体重。采用RT-PCR检测UCP 1(BAT)、UCP 3(腓肠肌)和食欲素(下丘脑)mRNA的表达。3周后,利培酮治疗的小鼠比PLA治疗的小鼠消耗更多的食物(p=0.050),体重增加更多(p=0.0001)。在给药的最初2天内,给药对活动(p=0.046)有急性影响,但对体温无影响(p=0.290)。在3周的治疗期间,与对照组相比,利培酮治疗组小鼠的平均核心体温在光照期较高(p=0.0001),在黑暗期倾向于较高(p=0.057)。在黑暗阶段,利培酮治疗小鼠的活动水平低于对照组(p=0.006);在光照阶段,活动无差异(p=0.47)。与对照组相比,利培酮治疗组小鼠中UCP 1(p<0.01)和UCP 3(p<0.05)mRNA表达更高,而利培酮治疗组小鼠中食欲素mRNA表达更低(p<0.01)。这些结果表明,利培酮诱导的小鼠体重增加是能量摄入增加和活动减少的结果,而体温升高可能是食物摄入的产热效应和UCP 1,UCP 3升高以及下丘脑食欲素表达减少的结果。
Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW*day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p=0.050) and gained more weight (p=0.0001) than PLA-treated mice after 3 weeks. During the initial 2-days of treatment, there was an acute effect of treatment on activity (p=0.046), but not body temperature (p=0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p=0.0001), and tended to be higher during the dark phase (p=0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p=0.006); there were no differences in activity during the light phase (p=0.47). UCP1 (p<0.01) and UCP3 (p<0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p<0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.
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