Living in a dangerous world: the shaping of behavioral profile by early environment and 5-HTT genotype

Heiming RS, Jansen F, Lewejohann L, Kaiser S, Schmitt A, Lesch KP and Sachser N

Abstract

Anxiety and anxiety disorders are infl uenced by both, environmental and genetic factors.One genetic factor under scrutiny for anxiety disorders is the genetically encoded variationof the serotonin transporter (5-HTT). The aim of this study was to elucidate the effects of athreatening environment during early phases of life on anxiety-like (ANX) and exploratorybehavior (EXP) in adult mice, varying in serotonin transporter (5-HTT) genotype. For thispurpose, pregnant and lactating 5-HTT +/- dams were repeatedly exposed to olfactorycues of unfamiliar adult males by introducing small amounts of soiled bedding to theirhome cage. These stimuli signal the danger of infanticide and simulate a threateningenvironment. Control females were treated with neutral bedding. The offspring (5-HTT +/+,+/-, -/-) were examined for their ANX and EXP. The main results were: (1) a main effect ofgenotype existed, with 5-HTT -/- showing higher levels of ANX and lower levels of EXPthan 5-HTT +/- and wildtypes. (2) When mothers had lived in a threatening environment,their offspring showed increased ANX and reduced EXP compared to controls. (3) Theseeffects were most pronounced in 5-HTT -/- mice. By applying a new ecologically relevantparadigm we conclude: If 5-HTT +/- mothers live in a threatening environment duringpregnancy and lactation, their offspring behavioral profi le will, in principle, be shaped in anadaptive way preparing the young for an adverse environment. This process is, however,modulated by 5-HTT genotype, bearing the risk that individuals with impaired serotonergicneurotransmission (5-HTT -/-) will develop an exaggerated, potentially pathological level ofanxiety from gene × environment interactions.