Effects of Mild Early Life Stress on Abnormal Emotion-related Behaviors in 5-HTT Knockout Mice

Abstract

A low-expressing polymorphic variant of the serotonin transporter (5-HTT) gene has been associated with emotional disorders in humans and non-human primates following exposure to early life trauma. 5-HTT gene knockout (KO) mice exhibit increased anxiety- and depression-related behaviors, and provide a model to study interactions between 5-HTT gene variation and early life stress. The present study assessed the effects of postnatal footshock stress on the development of emotion-related behaviors in 5-HTT KO mice. Results showed that 5-HTT KO mice displayed a profile of suppressed exploratory behavior and increased anxiety-like behavior in the light/dark, elevated plus-maze and open field tests, as well as increased depression-related behavior in the forced swim test following repeated exposure to the test. Postnatal exposure to footshock stress did not affect emotion-related behaviors in non-mutant C57BL/6J mice or modify phenotypic abnormalities in 5-HTT KO. Data provide further evidence of emotional abnormalities following genetic disruption of the 5-HTT.

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…However, the 5-HTT knockout status does not interact with exposure to mild postnatal foot-shock stress. 25 Interactions with more chronic and severe forms of stress, such as maternal separation, remain to be explored. Thus, while the mouse knockout model confirms the association of 5-HTT with anxious and depressive traits and impaired adaptation to repetitive stress it has so far not provided evidence supporting the interaction with early life stressors.…”

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

“…A loss of 5-HT1A-R binding and autoreceptor function in these knockout mice further exacerbates ECF levels for the reasons discussed below (Bouali et al, 2003;Fabre et al, 2000;Gobbi et al, 2001;Li et al, 1999Li et al, , 2000Li et al, , 2004. These neurochemical changes are associated with an increase in anxiety-like behavior in a battery of the standard test assays (Ansorge et al, 2004;Carroll et al, 2007;Fox et al, 2007;Holmes et al, 2002aHolmes et al, , 2003bHolmes et al, , 2003cKalueff et al, 2007;Lira et al, 2003;Zhao et al, 2006a). Interestingly, transgenic overexpression of the SERT gene produces the opposite phenotype-i.e., reduced anxiety-like behavior (Jennings et al, 2006).…”

Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome

“…To rule out this parameter as a potential confounding factor for the interpretation of the Morris water maze experiments, animals were first subjected to the open-field test (28). In this paradigm, mice are placed in a novel and bright arena.…”