Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Pieter Schippers (Donderd series 297)

20 October 2017

Promotor: prof. dr. T. Kozicz, copromotors: dr. J. Homberg en dr. M. Henckens

Smart coping: serotonin transporter gene variation and environment interact in determining the behavioral adaptation to stress

The aim of this thesis was to investigate how serotonin transporter (5-HTT) gene variation and environment interact in determining the behavioral adaptation to stress. We investigated whether variation in 5-HTT expression modulates uncontrollable stress (USt) induced adaptations in emotional behavior by assessing the effects of a severe USt experience on subsequent extinction of conditioned fear 5-HTT-/- and wild type rats. While fear extinction and recall were not affected by the USt in wild type animals, USt normalized fear extinction recall in 5-HTT-/- rats. Next, we explored how abolishment of the 5-HTT affects controllability-dependent stressor-induced activation of the DRN and prefrontal cortex (PFC). We found that active avoidance learning was improved as a result of 5-HTT abolishment. Serotonergic activation in the DRN was controllability-dependent in wild type, but not 5-HTT-/- animals, but activation of the PFC was dependent only on stressor type, not genotype. Subsequently, we investigated whether 5-HTT affects the flexibility of stress coping response acquisition across different stressor types in chapter 5. To this end, we assessed behavior in 5-HTT-/- and wild type rats during subsequent administration of fear- or sham- conditioning and a signaled shock active avoidance learning paradigm, in which the conditioned stimulus (CS) from the fear- or sham-conditioning was used to signal incoming shocks. Subsequently, we measured the behavioral response to that CS in a novel, neutral context. During the re-exposure to the CS in a novel context, we found that irrespective of sham- or fear-conditioning, CS-induced freezing was reduced in 5-HTT-/- animals compared to wild type animals. In conclusion, experimental observations here and elsewhere support the notion that 5-HTT-/- animals exert a coping profile that is not necessarily slanted towards maladaptive, passive coping, but instead may be better adjusted to the situational demands, and therefore in fact more adaptive than that seen in wild types.