Unexpected effects of early-life adversity and social enrichment on the anxiety profile of mice varying in serotonin transporter genotype

• Mice varying in 5-HTT expression experienced different early environments.
• Abolished 5-HTT expression reduced measures of state as well as trait anxiety.
• Early environment affected only trait but not state anxiety.
• Moderately adverse conditions lowered trait anxiety compared to social enrichment.
• Thus, anxiety profiles can be affected by the early environment and 5-HTT genotype.

Developmental mechanisms that shape behaviour are under environmental as well as genetic influence, commonly referred to as gene-by-environment interaction (GxE). Here, we compared the role of different early environments – adverse, standard, and enriched – for the modulation of the anxiety profile in mice varying in serotonin transporter (5-HTT) genotype. Early-life adversity was simulated by exposing lactating 5-HTT +/− dams to soiled bedding of unfamiliar males (UMB), signalling the danger of infanticide. An enriched early environment was established by communal nesting (CN). 5-HTT +/− females of a third group were housed under standard nesting conditions (SN) of individual nesting. The offspring (5-HTT +/+, 5-HTT +/−, and 5-HTT −/−) were analyzed for anxiety-like and exploratory behaviour in a battery of tests. The main findings were: (1) Maternal care was reduced in UMB compared to CN dams. (2) There was no significant variation in state anxiety levels between UMB, SN, and CN offspring. (3) UMB offspring showed significantly lower levels of trait anxiety compared to CN offspring, while SN offspring were intermediate. (4) There was a significant main effect of genotype, with highest levels of state and trait anxiety in 5-HTT −/− mice. The findings corroborate that anxiety profiles in mice can be affected by both early environmental conditions and 5-HTT genotype. Notably, state and trait anxiety of an individual can independently be affected by the early environment.