Social Bonding: A Matter of Serotonin Transporter Gene Variation and Oxytocin Neurotransmission?
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2014-02-18
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en
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One genetic factor influencing social coping style is the short (''s") variant of the human Serotonin-transporter-linked polymorphic region (5-HTILPR) that has been associated with higher sensitivity to social stress in a Gene-Environment interaction fashion (GxE). Besides the GxE concept, 5-HTTLPR might be related to the Gene-Environment correlation (rGE) concept, according to which, since our social environment is shaped by our geneticallydetermined and inheritable behaviors, it is inheritable as well.
In our approach, the social behavior of male Wistar 5-HTT +/+ and 5-HTT -/- rats (with the latter modeling the s- carriers of the 5-HTILPR) is assessed during social interaction between 2 animals that are similar (homogenotype interaction) or different (hetorogenotype interaction) with reference to the 5-HTI genotype. Juvenile, adolescent and adult groups are separately tested considering that the nature of social interactions changes during development.
In line with previous studies in which 5-HTT-/- mice negatively altered their behavior when switched trom homogenotype to heterogenotype interaction, we hypothesized that, tor 5-HTI/- rats the formation or lack of social bands (bonding is expressed as social play and prosocial behavior) is influenced by the type of social interaction (homo- vs heterogenotype) reflecting a GxE effect and this effect is altered across ages.
Furthermore, taking into account previous reports showing 5-HTI-/- reduction of social play compared to 5-HTT +/+ rats during homogenotype interactions, we examined the hypothesis that the 5-HTT-/- genotype has a significant rGE effect, which can be reflected as increased influence of the 5-HTI-/- rats' behavior on their partners' social behavior and thus, their social environment.
Regarding the neural underpinnings of this behavioral profile it has been reported that 5-HTI/- animals display abnormally elevated corticotropine releasing factor (CRF) levels under stressful conditions. We are also interested in Oxytocin (OXT), an hormone known to enhance (pro)social behavior and reduce anxiety, since findings supporting a significant 5-HT-OXT interaction might suggest altered OXT neurotransmission in our animal model. Taken together, we hypothesize that in 5-HTT-/- rats the formation of social bands is characterized by increased OXT neurotransmission and lower CRF levels.
As expected, we observed a 5-HTT-/- GxE effect during adolescence, with the heterogenotype interaction decreasing prosocial behavior (reflecting a lack of bonding) and increasing self-grooming (indicative for anxiety). In adulthood, we observed 5-HTT-/- GxE effect on the duration of no- contact, which was increased in heterogenotype vs homogenotype condition, suggesting lack of bonding. lnterestingly, in juveniles, the 5-HTT-/GxE effect is expressed in an opposite direction, increasing social play (that can be considered as a bonding behavior) during heterogenotype compared to homogenotype interaction. Unfortunately, we were not able to understand the role of OXT-related activation in occurrence or lack of bonding due to anti- OXTR antibody inefficiency, but the correlation between the (lack of) bonding and anxiety and the CRF levels during social interaction is currently under statistica! investigation.
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Faculteit der Sociale Wetenschappen