Blanchard D Caroline
Pacific Biosciences Research Center, University of Hawaii, Manoa, Honolulu, HI, USA; Institute of Biomedical Sciences at the University of São Paulo, Sao Paulo, Brazil.
Neurosci Biobehav Rev. 2023 Jan;144:104947. doi: 10.1016/j.neubiorev.2022.104947. Epub 2022 Nov 4.
Anxiety and depression are highly prevalent behavior disorders, particularly in women. Recent preclinical work using animal models has been suboptimal in predicting the efficacy of drugs targeted at these conditions, suggesting a potential discrepancy between such models and the human disorders. Notably female animals tend to be equal to, or less responsive than, males in these tasks. A number of analyses suggest that mammalian defense patterns are complex: In addition to relatively discrete and immediate fight, flight, and freezing responses, a risk assessment pattern may occur in response to threat stimuli or situations with ambiguous elements. This pattern combines defensiveness with a number of cognition-linked behaviors such as sensory attention and orientation, approach, contact, and investigation of the potential threat. Studies measuring elements of this pattern suggest that female rats, and perhaps female mice, show higher levels than equivalent males. Higher female involvement may also occur in tasks involving learning/generalization/extinction of defensiveness to conditioned stimuli. Such findings are consonant with recent analyses of "female survival strategies" based on differential adaptiveness of cognitive components of defensiveness in females, due to the necessity of female care of offspring until they are independent. These data suggest the value of additional behavioral and functional analyses of cognitive aspects of defensive behavior; contributing to both an understanding of their underlying mechanisms, and providing more sensitive measures of drug responsivity for use with animal models.
焦虑和抑郁是非常普遍的行为障碍,在女性中尤为常见。最近使用动物模型的临床前研究在预测针对这些病症的药物疗效方面并不理想,这表明此类模型与人类疾病之间可能存在差异。值得注意的是,在这些任务中,雌性动物往往与雄性动物表现相当,或者比雄性动物反应更弱。多项分析表明,哺乳动物的防御模式很复杂:除了相对离散和即时的战斗、逃跑和僵住反应外,面对威胁刺激或具有模糊因素的情况时,可能会出现风险评估模式。这种模式将防御与一些与认知相关的行为结合在一起,如感官注意力和定向、接近、接触以及对潜在威胁的调查。测量这种模式要素的研究表明,雌性大鼠,或许还有雌性小鼠,比同等雄性表现出更高的水平。在涉及对条件刺激的防御性学习/泛化/消退的任务中,雌性的参与度也可能更高。这些发现与最近基于雌性防御认知成分的差异适应性对“雌性生存策略”的分析一致,因为雌性有必要照顾后代直到它们独立。这些数据表明对防御行为认知方面进行额外行为和功能分析的价值;这有助于理解其潜在机制,并为动物模型提供更敏感的药物反应测量方法。