title: Serotonin transporter genotype x construction stress interaction in rats.
abstract: 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.
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Schipper
authors.forename: Lourens J P
authors.initials: LJ
authors.lastname: Nonkes
authors.forename: Peter
authors.initials: P
authors.lastname: Karel
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D005160:Facility Design and Construction; D005260:Female; D055786:Gene Knockout Techniques; D005838:Genotype; D046353:Immobility Response, Tonic / Q000502:physiology; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012193:Reversal Learning / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins