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强迫游泳试验诱导大鼠内分泌和免疫变化:亚急性地昔帕明治疗的影响

Forced swim test-induced endocrine and immune changes in the rat: effect of subacute desipramine treatment.

作者信息

Connor T J, Kelly J P, Leonard B E

机构信息

Department of Pharmacology, University College, Galway, Ireland.

出版信息

Pharmacol Biochem Behav. 1998 Jan;59(1):171-7. doi: 10.1016/s0091-3057(97)00316-x.

Abstract

Previously it has been reported that forced swim test (FST) exposure activates the HPA-axis and produces alterations in both cellular and noncellular immunity in rats. Furthermore, there is evidence to suggest that pretreatment with antidepressants has a protective effect against FST-induced immune changes. The purpose of the present study was to examine the effect of subacute treatment with the tricyclic antidepressant desipramine (DMI, 5 and 10 mg/kg; I.P.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in the rat. DMI treatment at a dose of 10 mg/kg produced a significant reduction in immobility time in the FST, while the 5 mg/kg dose was ineffective. FST exposure produced a significant increase in serum corticosterone and a decrease in adrenal ascorbic acid concentrations, neither of which were significantly attenuated by DMI pretreatment. There was a slight but nonsignificant suppression of PHA-induced lymphocyte proliferation 15 min post-FST exposure. However, DMI treatment produced a significant increase in lymphocyte proliferation at this time point. FST exposure caused a reduction in the percentage of lymphocytes and an increase in the percentage of neutrophils in the peripheral blood; DMI treatment failed to significantly alter these stress-induced changes. There was a profound reduction in relative spleen weight observed in DMI-treated animals 120 min post-FST exposure and this was accompanied by an increase in circulating RBC concentrations. In conclusion, although the FST-induced behavioral changes were normalized by DMI treatment the peripheral aberrations induced by FST exposure (with the exception of lymphocyte proliferation) were not. In addition, DMI pretreatment induced stress-like changes in corticosterone, adrenal ascorbic acid and leucocyte subpopulations in the control animals.

摘要

此前有报道称,强迫游泳试验(FST)会激活大鼠的下丘脑-垂体-肾上腺(HPA)轴,并导致细胞免疫和非细胞免疫发生改变。此外,有证据表明,用抗抑郁药预处理对FST诱导的免疫变化具有保护作用。本研究的目的是检验三环类抗抑郁药地昔帕明(DMI,5和10 mg/kg;腹腔注射)亚急性治疗对FST中不动时间的影响,以及对FST诱导的大鼠内分泌和免疫参数变化的影响。10 mg/kg剂量的DMI治疗使FST中的不动时间显著缩短,而5 mg/kg剂量无效。FST暴露使血清皮质酮显著增加,肾上腺抗坏血酸浓度降低,DMI预处理均未使其显著减弱。FST暴露后15分钟,PHA诱导的淋巴细胞增殖有轻微但不显著的抑制。然而,此时DMI治疗使淋巴细胞增殖显著增加。FST暴露导致外周血淋巴细胞百分比降低,中性粒细胞百分比增加;DMI治疗未能显著改变这些应激诱导的变化。FST暴露后120分钟,观察到DMI治疗的动物相对脾重显著降低,同时循环红细胞浓度增加。总之,尽管DMI治疗使FST诱导的行为变化恢复正常,但FST暴露诱导的外周异常(淋巴细胞增殖除外)并未恢复正常。此外,DMI预处理在对照动物中诱导了皮质酮、肾上腺抗坏血酸和白细胞亚群的应激样变化。

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