Modulation of behavioural profile and stress response by 5-HTT genotype and social experience in adulthood

Behavioural profiles can be shaped by genotype and environmental factors during early phases of life. The aim of this study was to investigate whether anxiety-like behaviour, exploration and adrenocortical stress responses can be modulated by genotype and social experiences in adulthood. Male mice lacking the serotonin transporter gene which is under scrutiny for anxiety disorders were compared with heterozygous and wildtype controls. Concerning social experiences, the males of all three genotypes were provided with a winner or a loser experience in a resident-intruder paradigm on three consecutive days. Anxiety-like behaviour and exploration were recorded in the dark-light, elevated plus-maze and open-field test. To non-invasively assess adrenocortical activity, corticosterone metabolites were determined from feces. The main findings were: Repeated social experience, irrespective of winning or losing, elevated levels of anxiety-like behaviour and decreased exploration. In losers a distinct effect of genotype occurred, with homozygous knockout males showing more anxiety-like behaviour and less exploration than the other genotypes. In winners no genotype-dependent variation was found. Genotypes did not differ in basal stress hormone secretion. There was, however, a main effect of social experience with higher activation of the stress hormone system in losers than in winners. This effect was strongest in the heterozygous genotype. In conclusion, our data show that anxiety circuits retain their plasticity throughout adulthood and can be shaped by genotype and social experiences during this phase of life. Moreover, responsiveness towards negative life experiences is influenced significantly by the 5-HTT genotype.