TY - JOUR A1 - Spinelli, Simona A1 - Müller, Tanja A1 - Friedel, Miriam A1 - Sigrist, Hannes A1 - Lesch, Klaus-Peter A1 - Henkelman, Mark A1 - Rudin, Markus A1 - Seifritz, Erich A1 - Pryce, Christopher R. T1 - Effects of repeated adolescent stress and serotonin transporter gene partial knockout in mice on behaviors and brain structures relevant to major depression JF - Frontiers in Behavioral Neuroscience N2 - In humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype x developmental stress effect on brain structure and function is limited. Here, we investigated the effect of repeated stress exposure during adolescence in mice with partial knockout of the 5-HIT gene (HET) vs. wildtype (WT) on early-adulthood behavioral measures and brain structure [using magnetic resonance imaging (MRI)] relevant to human major depression. Behaviorally, adolescent stress (AS) increased anxiety and decreased activity and did so to a similar degree in HET and WT. In a probabilistic reversal learning task, HET-AS mice achieved fewer reversals than did HET-No-AS mice. 5-HIT genotype and AS were without effect on corticosterone stress response. In terms of structural brain differences, AS reduced the volume of two long-range white matter tracts, the optic tract (OT) and the cerebral peduncle (CP), in WT mice specifically. In a region-of-interest analysis, AS was associated with increased HC volume and HET genotype with a decreased frontal lobe volume. In conclusion, we found that 5-HIT and AS genotype exerted long-term effects on behavior and development of brain regions relevant to human depression. KW - mouse-brain KW - white-matter integrity KW - linked polymorphic region KW - C57BL/6 mice KW - lerned helplessness KW - 5-HTTLPR polymorphism KW - childhood maltreatment KW - rhesus macaques KW - 3-dimensional MRI KW - life stress Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122240 VL - 7 ER -