title: Prior fear conditioning does not impede enhanced active avoidance in serotonin transporter knockout rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Pieter
authors.initials: P
authors.lastname: Schipper
authors.affiliation: 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.
authors.forename: Marloes J A G
authors.initials: MJAG
authors.lastname: Henckens
authors.affiliation: 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.
authors.forename: Bart
authors.initials: B
authors.lastname: Borghans
authors.affiliation: 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.
authors.forename: Marlies
authors.initials: M
authors.lastname: Hiemstra
authors.affiliation: Anatomy Department, Centre for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Geert Grooteplein 21 (route 109), 6525 EZ Nijmegen, The Netherlands.
authors.forename: Tamas
authors.initials: T
authors.lastname: Kozicz
authors.affiliation: 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. Electronic address: judith.homberg@radboudumc.nl.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat
keywords: Active avoidance learning; Behavioural flexibility; Fear extinction; Serotonin transporter gene; Stress coping