Prior fear conditioning does not impede enhanced active avoidance in serotonin transporter knockout rats

Pieter Schipper, Marloes J.A.G. Henckens, Bart Borghans, Marlies Hiemstra, Tamas Kozicz, Judith R. Homberg

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalBehavioural Brain Research
StatePublished - May 30 2017


  • Active avoidance learning
  • Behavioural flexibility
  • Fear extinction
  • Serotonin transporter gene
  • Stress coping

ASJC Scopus subject areas

  • Behavioral Neuroscience


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