Kopp C, Vogel E, Misslin R
Universite Louis Pasteur, URA-CNRS 12, Laboratoire d'Ethologie et Neurobiologie, 7 rue de l'Université, Strasbourg 67000, France.
Behav Processes. 1999 Oct;47(3):161-74. doi: 10.1016/s0376-6357(99)00057-1.
Anxious behaviour constitutes one of the markers that best differentiated the 'non-emotional' C57BL/6 (C57) strain from the 'emotional' BALB/c (BALB) strain. Interestingly, C3H/He (C3H) mice, which possess a common genetic background to BALB, have also been found to be 'emotional' mice. The present study first illustrates that BALB and C3H mice exhibit a higher emotional level both in non-constraining situation (free-exploratory paradigm) and in a stressful one (light/dark choice test). Second, the present results confirmed the hypothesis that trait anxiety, modelled neophobic reactions in the free-exploratory paradigm, is related to GABA-benzodiazepine system rather than to the serotoninergic one, in contrast to state anxiety, modelled by the light/dark choice test. Like in BALB mice, chlordiazepoxide was able to counteract the neophobic responses in C3H mice confronted with the free-exploratory paradigm, in contrast to 8-OH-DPAT which did not modify C3H behaviour in this test. Conversely, both chlordiazepoxide and 8-OH-DPAT reduced anxious reactions of BALB and C3H mice in the light/dark choice test, showing that BALB and C3H mice are sensitive to serotonin-interacting drugs only when confronted with a stressful situation. Furthermore, chlordiazepoxide and 8-OH-DPAT were found to be devoid of anxiolytic-like effect in C57 mice. The lack of anxiolytic-like activity of these compounds in C57 mice can be related to the low basal level of emotional reactions of this strain. Finally, the present results showed that chronic stress was able to blunt general emotional level of mice in both experimental situations and that both BALB and C3H mice were more sensitive to chronic stress than C57 ones. In conclusion, BALB and C3H may be two strains of choice for testing potential anti-anxiety treatments which might be of great long-term benefit in the chronically anxious patients. Furthermore, these strains constitute interesting material for determining hereditary factors which presumably underlie the development of some chronic anxiety disorders. Finally, since C3H and BALB mice appeared particularly susceptible to chronic stress, it can be proposed that these strains may be a useful tool to examine the possible common origins of anxiety disorders and chronic stress-related disorders, such as certain forms of depression.
焦虑行为是区分“非情绪化”的C57BL/6(C57)品系和“情绪化”的BALB/c(BALB)品系的最佳标志之一。有趣的是,与BALB具有共同遗传背景的C3H/He(C3H)小鼠也被发现是“情绪化”小鼠。本研究首先表明,BALB和C3H小鼠在非约束情境(自由探索范式)和应激情境(明暗选择试验)中均表现出较高的情绪水平。其次,本研究结果证实了以下假设:在自由探索范式中以新物恐惧反应为模型的特质焦虑与GABA-苯二氮䓬系统有关,而非与5-羟色胺能系统有关,这与明暗选择试验所模拟的状态焦虑相反。与BALB小鼠一样,氯氮卓能够抵消C3H小鼠在自由探索范式中面对新物时的恐惧反应,而8-羟基二丙胺基四氢萘(8-OH-DPAT)在此试验中并未改变C3H小鼠的行为。相反,氯氮卓和8-OH-DPAT在明暗选择试验中均降低了BALB和C3H小鼠的焦虑反应,表明BALB和C3H小鼠仅在面对应激情境时才对5-羟色胺相互作用药物敏感。此外,发现氯氮卓和8-OH-DPAT对C57小鼠没有抗焦虑样作用。这些化合物在C57小鼠中缺乏抗焦虑样活性可能与该品系情绪反应的低基础水平有关。最后,本研究结果表明,慢性应激能够削弱两种实验情境中小鼠的总体情绪水平,且BALB和C3H小鼠比C57小鼠对慢性应激更敏感。总之,BALB和C3H可能是测试潜在抗焦虑治疗方法的两种理想品系,这些治疗方法可能对慢性焦虑患者有长期益处。此外,这些品系是确定可能构成某些慢性焦虑症发病基础的遗传因素的有趣材料。最后,由于C3H和BALB小鼠似乎对慢性应激特别敏感,因此可以认为这些品系可能是研究焦虑症和慢性应激相关疾病(如某些形式的抑郁症)可能的共同起源的有用工具。