title: Benefits of a "vulnerability gene"? A study in serotonin transporter knockout mice.
abstract: Over the past years, certain "vulnerability genes" have been identified that play a key role in the development of mood and anxiety disorders. In particular, a low-expressing variant of the human serotonin transporter (5-HTT) gene has been described that renders individuals more susceptible to adverse experience and hence to the development of psychiatric diseases. However, some authors have recently argued that lower 5-HTT expression not only increases vulnerability to adverse experiences, but also enhances susceptibility to beneficial experiences, thus promoting phenotypic plasticity. The aim of the present study was to assess the effects of 5-HTT expression on susceptibility to beneficial experience in a hypothesis-driven experimental approach. Using a well-established rodent model for the human polymorphism, male heterozygous 5-HTT knockout (HET) and 5-HTT wildtype (WT) mice were either provided with the beneficial experience of cohabitation with a female (mating experience) or kept as naïve controls in single-housing conditions. Following the experimental treatment, they were tested for their anxiety-like behaviour and exploratory locomotion in three widely used behavioural tests. Interestingly, while cohabitation reduced anxiety-like behaviour and increased exploratory locomotion in the open field test in HET mice, it did not affect WT mice, pointing to a genotype-dependent susceptibility to the beneficial experience. Thus, our results might support the view of the low expressing version of the 5-HTT gene as a "plasticity" rather than a "vulnerability" variant.
authors: Department of Behavioural Biology, University of Münster, Badestraße 13, 48149 Münster, Germany. Electronic address: niklas.kaestner@uni-muenster.de.
authors: Niklas
authors: N
authors: Kästner
authors: Department of Behavioural Biology, University of Münster, Badestraße 13, 48149 Münster, Germany.
authors: S Helene
authors: SH
authors: Richter
authors: Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics & Psychotherapy, University of Würzburg, Füchsleinstraße 15, 97070 Würzburg, Germany.
authors: Klaus-Peter
authors: KP
authors: Lesch
authors: Department of Behavioural Biology, University of Münster, Badestraße 13, 48149 Münster, Germany.
authors: Rebecca S
authors: RS
authors: Schreiber
authors: Department of Behavioural Biology, University of Münster, Badestraße 13, 48149 Münster, Germany.
authors: Sylvia
authors: S
authors: Kaiser
authors: Department of Behavioural Biology, University of Münster, Badestraße 13, 48149 Münster, Germany.
authors: Norbert
authors: N
authors: Sachser
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D006799:Housing, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009483:Neuropsychological Tests; D011897:Random Allocation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics*; D012726:Sexual Behavior, Animal / Q000502:physiology
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse
keywords: Anxiety-like behavior; Beneficial experience; Gene-by-environment interaction; Mice; Serotonin transporter