Harro Jaanus
Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Ravila 14A Chemicum, 50411, Tartu, Estonia.
Behav Brain Res. 2018 Oct 15;352:81-93. doi: 10.1016/j.bbr.2017.10.016. Epub 2017 Oct 16.
Measurement of anxiety is desirable for the benefit of drug development and understanding the brain function and mental well-being. Animal models offer the advantages of detailed neurobiological analysis, experimental manipulation of specific components in the brain circuits that underlie psychopathology, and the possibility of screening novel drugs with clinical potential. A large variety of animal models of anxiety and screening tests of anxiolytics is currently in use. While their value in advancing the knowledge and predicting therapeutic success of drugs is unquestionable, the expectations have grown much higher, and the frustration over absence of novel successful drug concepts is rising. It is argued that the multitude of factors that can interfere with animal behaviour in anxiety tests, and the complexity of neurobiology of the various anxiety disorders, present high demands on validation of each anxiety test within each specific laboratory condition. Anxiety models should be explicitly related to a theoretical paradigm on underlying neurobiology, because there is a diversity in concepts, and validation of the model and the selection of behavioural readouts is critically dependent on the neurobiological model. Environmental conditions during the model production and anxiety testing need more attention, including the less considered factors such as ultrasounds. More attention is required to the differences in anxiety neurobiology between males and females, and inter-individual differences in coping strategies.
为了药物研发以及理解脑功能和心理健康,焦虑测量是很有必要的。动物模型具有详细神经生物学分析、对构成精神病理学基础的脑回路特定成分进行实验操纵以及筛选具有临床潜力新药的可能性等优势。目前正在使用各种各样的焦虑动物模型和抗焦虑药筛选试验。虽然它们在推进知识和预测药物治疗成功方面的价值是毋庸置疑的,但人们的期望已经高得多,并且对缺乏新的成功药物概念的挫败感正在上升。有人认为,在焦虑测试中会干扰动物行为的众多因素以及各种焦虑症神经生物学的复杂性,对在每个特定实验室条件下验证每种焦虑测试提出了很高的要求。焦虑模型应该与潜在神经生物学的理论范式明确相关,因为概念存在多样性,并且模型的验证和行为读数的选择严重依赖于神经生物学模型。模型构建和焦虑测试期间的环境条件需要更多关注,包括超声等较少考虑的因素。需要更多关注雄性和雌性之间焦虑神经生物学的差异以及应对策略的个体差异。