Effects of acute and chronic treatment with fluoxetine on stress-induced hyperthermia in telemetered rats and mice
Effects of acute and chronic treatment with fluoxetine on stress-induced hyperthermia in telemetered rats and mice
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DOI：
10.1016/j.ejphar.2007.02.063
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发表时间：
2007-06-14
影响因子：
5
通讯作者：
Hutson, Peter H.
中科院分区：
文献类型：
--
作者：
Conley, Rachel K.;Hutson, Peter H.
临床前和临床证据表明，在长期服用选择性肌钙蛋白再摄取抑制剂氟西汀后，可以观察到抗焦虑效果。相比之下，急性治疗可能会增加焦虑的迹象。本研究观察了急性和慢性给予氟西汀对大鼠和小鼠焦虑的一种生理指标--应激性体温升高的影响，方法是用无线电遥测法记录核心温度、运动活动和行为学相关的应激源，以唤起高热反应。在这两个物种中，苯二氮卓类激动剂氯氮卓酮在剂量(5 mg/kg i.p.大鼠，10 mg/kg灌胃。对运动活动没有显著影响。同样，在这两个物种中，长期(21天)使用氟西汀治疗可以减弱高热反应，而不会显著影响运动活动。然而，急性氟西汀引起了物种特异性效应。因此，在小鼠中，氟西汀(20 mg/kg，P.O.)不影响应激性体温升高和活动。与缺乏抗焦虑或引起焦虑的活动相一致。相反，在大鼠中，氟西汀(10 mg/kg ip)。在没有应激的情况下，导致了显著的基线体温降低，混淆了进一步的解释。总之，小鼠应激性体温升高不受急性治疗的影响，而慢性氟西汀治疗则显著减轻。然而，在大鼠中，长期服用氟西汀显著降低了应激引起的体温过高，而急性治疗的效果与没有应激的体温下降相混淆。总之，这些观察结果支持这样的观点，即长期服用氟西汀可以缓解焦虑；然而，应激诱导的体温升高试验并没有揭示急性服用氟西汀对大鼠或小鼠的焦虑效应。(C)2007爱思唯尔B.V保留所有权利。
Preclinical and clinical evidence suggests that anxiolytic effects are observed after chronic administration of the selective scrotonin reuptake inhibitor fluoxetine. In contrast, acute treatment may increase signs of anxiety. The present study examined the effects of acute and chronic administration of fluoxetine on a physiological measure of anxiety, stress-induced hyperthermia, in rats and mice using radiotelemetry to record core temperature and locomotor activity and ethologically relevant stressors, to evoke the hyperthermic response. In both species, the benzodiazepine agonist chlordiazepoxide reduced stress-induced hyperthermia at doses (5 mg/kg i.p. rat, 10 mg/kg p.o. mouse) that had no significant effect on locomotor activity. Similarly, in both species, chronic (21 days) treatment with fluoxetine attenuated the hyperthermic response without significantly affecting locomotor activity. However, acute fluoxetme elicited species-specific effects. Thus in mice, stress-induced hyperthermia and activity were unaffected by fluoxetine (20 mg/kg p.o.) consistent with a lack of anxiolytic or anxiogenic activity. In contrast, in rats, fluoxetine (10 mg/kg i.p.) caused a significant baseline hypothermia in the absence of stress, confounding further interpretation. In conclusion, stress-induced hyperthermia in mice was unaffected by acute treatment and significantly reduced by chronic treatment with fluoxetine. However, in rats chronic administration of fluoxetine significantly reduced stress-induced hyperthermia while the effects of acute treatment were confounded by a decrease in body temperature in the absence of stress. Together, these observations support the view that chronic administration of fluoxetine is anxiolytic; however, the stress-induced hyperthermia assay does not reveal anxiogenic effects of acute administration of fluoxetine in rats or mice. (c) 2007 Elsevier B.V All rights reserved.