Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat
Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat
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DOI：
10.1007/s002130000400
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发表时间：
2000-05-01
影响因子：
3.4
通讯作者：
Rochford, J
中科院分区：
文献类型：
--
作者：
Mar, A;Spreekmeester, E;Rochford, J
其治疗效果的发挥仍不得而知。目前认为对压力刺激的反应会导致情感障碍的发作和病程。据推测，抗抑郁药可能通过改善对挑战性生活事件的反应模式来发挥作用，例如反应和/或习惯过程。目的：使用嗅球切除术（OBX）大鼠模型，本研究检查了各种抗抑郁药对评估对新刺激的反应的行为测试中的反应性和习惯性测量的影响。方法：假手术大鼠和 OBX 大鼠每天接受 21 次注射氟西汀 (10 mg/kg)、阿米替林 (10 mg/kg)、地昔帕明 (10 mg/kg)、丁螺环酮 (3 mg/kg) 或媒介物。最后一次注射后四十八小时，在旷场、高架十字迷宫和惊吓装置中对动物进行测试。对于每个测试，收集时间序列数据并与指数随机效应模型拟合，其中估计参数评估行为反应性和习惯性。结果：相对于假手术对照组，OBX 大鼠在开放区域中表现出增加的总运动活动，并且在高架十字迷宫中表现出增加的开臂行为。通过与硫酸锌处理的嗅觉丧失对照相比，这些 OBX 诱导的增加归因于嗅觉丧失引起的初始反应性的增强和平均习惯率的减弱。长期抗抑郁治疗并未将 OBX 大鼠的嗅觉缺失相关初始反应水平降低至假手术对照组。相反，抗抑郁药通过提高习惯率来激发其恢复作用。结论：这些发现表明，抗抑郁药可以通过更有效地适应新刺激来恢复正常反应。
exert their therapeutic effects remain unknown. Responses to stressful stimuli are currently thought to contribute to the onset and course of affective disorders. It has been postulated that antidepressants might act by ameliorating response patterns to challenging life events, such as processes of reactivity and/or habituation. Objective: Using the olfactory bulbectomy (OBX) rat model, this study examined the effects of various antidepressants on measures of reactivity and habituation in behavioral tests assessing responses to novel stimuli. Methods: Sham-operated and OBX rats received 21 daily injections of fluoxetine (10 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), buspirone (3 mg/kg), or vehicle. Forty-eight hours after the last injection, animals were tested in the open field, elevated plus maze, and startle apparatus. For each test, time series data were collected and fit with exponential random effects models, in which estimated parameters assessed behavioral reactivity and habituation. Results: Relative to sham controls, OBX rats displayed increased total locomotor activity in the open field and exhibited increased open arm behavior in the elevated plus maze. Through comparison with zinc sulfate-treated anosmic controls, these OBX-induced increases were attributed to both an augmentation of initial reactivity due to anosmia and an attenuation of the average rate of habituation. Chronic antidepressant treatment did not reduce the anosmia-related initial reactivity levels of OBX rats to that of sham controls. Rather, the antidepressants evoked their restorative effects by increasing the rate of habituation. Conclusions: These Findings suggest that antidepressants restore normal responding by permitting more effective adaptation to novel stimuli.