LVR Klinikum Düsseldorf, Kliniken der Heinrich-Heine-Universität, Düsseldorf, Germany.
Clinics (Sao Paulo). 2010;65(9):885-94. doi: 10.1590/s1807-59322010000900012.
The aim of our study was to investigate the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats.
From the age of 13 to 18 weeks, three groups of 20 animals were fed an average dose of 3.5 + 0.03 mg/ kg body weight (BW) haloperidol; 30.6 + 0.22 mg/kg BW clozapine; or 14.9 + 0.13 mg/kg BW ziprasidone in ground food pellets containing 15% fat. Twenty control animals received no drugs. Blood samples were taken at week 14, 16, and 19. Locomotor activity and exploratory behavior were measured using the alcove test at weeks 15 and 17. The expression of the hypothalamic leptin receptor in rat brains was determined by using a Western blot.
Rats medicated with haloperidol and ziprasidone showed a significantly decreased percentage weight gain and food consumption. We observed no differences in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, we found no changes in the leptin blood concentrations among the four groups or animals within each group. Moreover, we did not find specific differences in hypothalamic leptin receptor expression among the groups.
We concluded that in male Wistar rats during this treatment period, the tested drugs did not act directly on the leptin regulatory system. We recommend further studies using long-term treatment of different rat strains.
我们的研究旨在探讨典型和非典型抗精神病药物对雄性 Wistar 大鼠血液中瘦素浓度和下丘脑受体表达变化的影响。
从 13 到 18 周龄起,三组 20 只动物分别喂食平均剂量为 3.5+0.03mg/kg 体重的氟哌啶醇;30.6+0.22mg/kg 体重的氯氮平;或 14.9+0.13mg/kg 体重的齐拉西酮,这些药物添加在含有 15%脂肪的地面食物丸中。20 只对照动物未给予药物。在第 14、16 和 19 周采集血样。在第 15 和 17 周使用壁龛试验测量运动和探索行为。使用 Western blot 确定大鼠大脑下丘脑瘦素受体的表达。
接受氟哌啶醇和齐拉西酮治疗的大鼠体重增加百分比和食物消耗明显减少。我们在壁龛试验中没有观察到差异,但氟哌啶醇组的运动活性显著降低。除氯氮平和齐拉西酮组的大鼠外,在药物应用 2 周后,我们没有发现四组之间或每组内的血液瘦素浓度有变化。此外,我们没有发现各组下丘脑瘦素受体表达有特定差异。
我们得出的结论是,在雄性 Wistar 大鼠的治疗期间,测试的药物没有直接作用于瘦素调节系统。我们建议使用不同大鼠品系进行长期治疗的进一步研究。