Schipper Pieter, Henckens Marloes J A G, Borghans Bart, Hiemstra Marlies, Kozicz Tamas, Homberg Judith R
Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Geert Grooteplein 21 (route 126), 6525 EZ Nijmegen, The Netherlands.
Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Geert Grooteplein 21 (route 126), 6525 EZ Nijmegen, The Netherlands; Anatomy Department, Centre for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Geert Grooteplein 21 (route 109), 6525 EZ Nijmegen, The Netherlands.
Behav Brain Res. 2017 May 30;326:77-86. doi: 10.1016/j.bbr.2017.02.044. Epub 2017 Mar 7.
Stressors can be actively or passively coped with, and adequate adaption of the coping response to environmental conditions can reduce their potential deleterious effects. One major factor influencing stress coping behaviour is serotonin transporter (5-HTT) availability. Abolishment of 5-HTT is known to impair fear extinction but facilitates acquisition of signalled active avoidance (AA), a behavioural task in which an animal learns to avoid an aversive stimulus that is predicted by a cue. Flexibility in adapting coping behaviour to the nature of the stressor shapes resilience to stress-related disorders. Therefore, we investigated the relation between 5-HTT expression and ability to adapt a learned coping response to changing environmental conditions. To this end, we first established and consolidated a cue-conditioned passive fear response in 5-HTT and wildtype rats. Next, we used the conditioned stimulus (CS) to signal oncoming shocks during signalled AA training in 5-HTT and wildtype rats to study their capability to acquire an active coping response to the CS following fear conditioning. Finally, we investigated the behavioural response to the CS in a novel environment and measured freezing, exploration and self-grooming, behaviours reflective of stress coping strategy. We found that fear conditioned and sham conditioned 5-HTT animals acquired the signalled AA response faster than wildtypes, while prior conditioning briefly delayed AA learning similarly in both genotypes. Subsequent exposure to the CS in the novel context reduced freezing and increased locomotion in 5-HTT compared to wildtype rats. This indicates that improved AA performance in 5-HTT rats resulted in a weaker residual passive fear response to the CS in a novel context. Fear conditioning prior to AA training did not affect freezing upon re-encountering the CS, although it did reduce locomotion in 5-HTT rats. We conclude that independent of 5-HTT signalling, prior fear conditioning does not greatly impair the acquisition of subsequent active coping behaviour when the situation allows for it. Abolishment of 5-HTT results in a more active coping style in case of novelty-induced fear and upon CS encounter in a novel context after AA learning.
应激源可以通过主动或被动的方式应对，而应对反应对应激环境条件的充分适应能够降低其潜在的有害影响。影响应激应对行为的一个主要因素是血清素转运体（5-HTT）的可用性。已知消除5-HTT会损害恐惧消退，但会促进信号主动回避（AA）的习得，这是一种行为任务，动物学会避免由线索预测的厌恶刺激。将应对行为适应应激源性质的灵活性塑造了对应激相关障碍的恢复力。因此，我们研究了5-HTT表达与将习得的应对反应适应不断变化的环境条件的能力之间的关系。为此，我们首先在5-HTT大鼠和野生型大鼠中建立并巩固了线索条件性被动恐惧反应。接下来，我们在5-HTT大鼠和野生型大鼠的信号AA训练期间使用条件刺激（CS）来预示即将到来的电击，以研究它们在恐惧条件化后对CS获得主动应对反应的能力。最后，我们在新环境中研究了对CS的行为反应，并测量了僵住、探索和自我梳理等反映应激应对策略的行为。我们发现，恐惧条件化和假条件化的5-HTT动物比野生型动物更快地获得了信号AA反应，而在两种基因型中，先前的条件化同样短暂地延迟了AA学习。与野生型大鼠相比，随后在新环境中接触CS会降低5-HTT大鼠的僵住程度并增加其运动。这表明5-HTT大鼠中AA表现的改善导致在新环境中对CS的残余被动恐惧反应较弱。在AA训练之前进行恐惧条件化不会影响再次遇到CS时的僵住程度，尽管它确实降低了5-HTT大鼠的运动。我们得出结论，在情况允许时，与5-HTT信号无关，先前的恐惧条件化不会极大地损害随后主动应对行为的习得。在新奇诱导的恐惧情况下以及在AA学习后在新环境中遇到CS时，消除5-HTT会导致更积极的应对方式。
