Serotonin transporter genotype x construction stress interaction in rats

A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are highly responsive to early life, but also adult external stressors, albeit conflicting data have been obtained. In our study on emotion and cognition using homozygous 5-HTT knockout (5-HTT−/−) and wild-type (5-HTT+/+) rats we have been confronted with animal facility construction, which were associated with severe lifetime stress (noise and vibrations). To assess the impact of construction stress on well-established 5-HTT−/− rat phenotypes we conducted ad hoc analyses of 5-HTT−/− and 5-HTT+/+ rats that grew up before and during the construction. The reproductive capacity of the parents of the experimental 5-HTT+/− rats was significantly decreased. Further, 5-HTT−/− anxiety-related phenotypes in the elevated plus maze and social interaction tests were abolished after construction noise exposure, due to increased anxiety in 5-HTT+/+ rats and decreased anxiety in 5-HTT−/− rats (social interaction test only). In addition, reversal learning was improved in 5-HTT+/+ and, to a milder extent, decreased in 5-HTT−/− rats. Finally, construction stress genotype-independently increased behavioural despair in the forced swim test. In conclusion, severe construction stress induces 5-HTT genotype-dependent ‘for-better-and-for-worse’ effects. These data importantly contribute to the understanding of 5-HTT gene x environment interactions and show the risk of losing genotype effects by construction stress.

► Construction stress abolishes genotype type-dependent phenotypes. ► Construction stress affects rat behaviour in a ‘for-better-and-worse’ manner. ► This effect is dependent on serotonin transporter knockout genotype.