Vigliecca Nora Silvana, Molina Silvia Cristina, Peñalva Marisa Carola
Consejo Nacional de Investigaciones Científicas y Técnicas de la Argentina (CONICET) y Servicio de Neurología y Neurocirugía del Hospital Córdoba, Argentina.
J Pharmacol Toxicol Methods. 2007 Jan-Feb;55(1):49-57. doi: 10.1016/j.vascn.2006.02.008. Epub 2006 Feb 28.
Clinical studies have shown that some antidepressants may be more efficient than benzodiazepines to alleviate anxiety associated with panic disorders; however, operant conflict procedures in rats developed so far seem not particularly able to model human anxiety sensitive to antidepressant treatments. Previous panic models with learned responses did not statistically subtract the effect of confounding factors from the variable of interest.
Undernourished rats were selected due to their behavioral and neurobiological resemblance to human patients suffering from panic disorder. The Geller-Seifter paradigm represented the stressful environmental condition in adult life. Desipramine (10 mg/kg/day) or saline were administered IP during 7 days under a cross over design (N=10). Five daily 15 min-operant sessions were carried out on each experiment. Unpunished, unrewarded and punished operant behavioral periods were identical both in their duration and in their reward system (the FR1 schedule) in order to measure response suppression, which has not been considered in previous studies with the Geller-Seifter paradigm. The dependent variable was the difference between comparable unpunished and punished periods.
A significant Diet x Drug interaction was observed in the dependent variable, which represented the level of "suppression/suppression release" induced by treatments.
Compared to control rats, deprived rats showed a significant and selective anticonflict effect of desipramine on the stressful and complex operant performance. The animal model of perinatally protein-deprived rats along with the Geller-Seifter's operant behavioral paradigm may represent a more sensitive approach to model human anxiety sensitive to antidepressant treatments by considering the combined impact of both early biological trauma and adult learned experiences under the same design.
临床研究表明，在缓解与惊恐障碍相关的焦虑方面，某些抗抑郁药可能比苯二氮䓬类药物更有效；然而，迄今为止在大鼠中建立的操作性冲突程序似乎并不能特别有效地模拟对抗抑郁治疗敏感的人类焦虑。先前具有习得反应的惊恐模型并未从感兴趣的变量中统计学地减去混杂因素的影响。
选择营养不良的大鼠是因为它们在行为和神经生物学上与患有惊恐障碍的人类患者相似。盖勒 - 西弗特范式代表成年生活中的应激环境条件。采用交叉设计（N = 10），在7天内腹腔注射地昔帕明（10毫克/千克/天）或生理盐水。每个实验每天进行5次15分钟的操作性实验。无惩罚、无奖励和有惩罚的操作性行为期在持续时间和奖励系统（固定比率1程序）方面均相同，以便测量反应抑制，而先前使用盖勒 - 西弗特范式的研究中并未考虑这一点。因变量是可比的无惩罚期和有惩罚期之间的差异。
在因变量中观察到显著的饮食×药物相互作用，该因变量代表治疗引起的“抑制/抑制释放”水平。
与对照大鼠相比，剥夺饮食的大鼠显示地昔帕明对应激性和复杂的操作性表现具有显著且选择性的抗冲突作用。围产期蛋白质缺乏大鼠的动物模型以及盖勒 - 西弗特的操作性行为范式，通过在同一设计中考虑早期生物创伤和成年习得经验的综合影响，可能代表一种更敏感的方法来模拟对抗抑郁治疗敏感的人类焦虑。
