A depressive phenotype induced by Bacille Calmette Guerin in 'susceptible' animals: sensitivity to antidepressants
A depressive phenotype induced by Bacille Calmette Guerin in 'susceptible' animals: sensitivity to antidepressants
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DOI：
10.1007/s00213-012-2923-6
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Clark, Janet A.
中科院分区：
文献类型：
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作者：
Platt, Brian;Schulenberg, Janet;Clark, Janet A.
慢性炎症 BCG 模型中的抑郁表型尚未进行药理学表征。本研究旨在表征 BCG 模型并建立其对氟西汀、地昔帕明和地西泮的药理学敏感性。给 CD-1 小鼠注射卡介苗 (BCG)，并测量体重、运动活性和悬尾试验 (TST) 中的不动性。在实验结束时对脾脏重量、血浆细胞因子和肺吲哚胺-2,3-双加氧酶mRNA进行评估。在幼稚 CD-1 小鼠中进行了急性氟西汀和地昔帕明的药理学研究，以使用 TST 确定剂量，并在运动试验中进行以确定地西泮的非镇静剂量。 BCG 模型的药理学敏感性特征是通过评估 BCG 治疗后 6 天的运动活性并测量治疗后 7 天在存在或不存在氟西汀 (56 mg/kg)、地昔帕明 (20 mg/kg) 或地西泮 (1 mg/kg) 的情况下的不动性来完成的。 10% 至 30% 的 BCG 治疗小鼠没有表现出不动性增加，并被称为“弹性”尽管有证据表明免疫系统被激活，但卡介苗仍引起行为改变。 BCG“易感”小鼠表现出 TST 不动性增加和运动活动缺陷。 BCG 敏感小鼠的不动性增加会被急性氟西汀和地昔帕明减弱，而地西泮会加剧。这种慢性炎症的 BCG 模型中的抑郁表型对抗抑郁药敏感，并且与临床报告一致，表明免疫治疗前帕罗西汀预处理可以预防精神症状的发展。
The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized.This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam.CD-1 mice were dosed with Bacille Calmette-Gu,rin (BCG) and measures of body weight, locomotor activity, and immobility in the tail suspension test (TST) were made. Spleen weight, plasma cytokines, and lung indoleamine-2,3-dioxygenase mRNA assessments were made at experiment termination. Pharmacological studies with acute fluoxetine and desipramine were done in na < ve CD-1 mice to establish doses using the TST and in a locomotor assay to establish a nonsedating dose of diazepam. Characterization of the pharmacological sensitivity of the BCG model was done by assessing locomotor activity 6 days post BCG treatment and measuring immobility at 7 days post treatment in the presence or absence of fluoxetine (56 mg/kg), desipramine (20 mg/kg), or diazepam (1 mg/kg).Ten to 30 % of BCG-treated mice did not exhibit an increase in immobility and were termed "resilient" to BCG-induced behavioral changes despite evidence of an activated immune system. BCG-"susceptible" mice exhibited increased immobility in TST and deficits in locomotor activity. The increased immobility in BCG-susceptible mice was attenuated by acute fluoxetine and desipramine, and exacerbated by diazepam.The depressive phenotype in this BCG model of chronic inflammation is sensitive to antidepressants and consistent with clinical reports showing that paroxetine pretreatment prior to immunotherapy can prevent the development of psychiatric symptoms.