The Flinders rat model of depression: gene-environment interaction and antidepressant effects by proteomic analysis.

The Flinders Sensitive Line (FSL) has been proposed as a rat model for depression, due to its ability to mimic several features of the human disease. With the aim of investigating gene-environment interaction, we have examined the impact of an early life stress, such as maternal separation, and the effect of antidepressant treatment on the hippocampus of FSL and their controls, the Flinders Resistant Line (FRL). 2D-gel proteomics was selected as an unbiased approach for wide-scale analysis of hippocampal protein expression. This project is part of the GENDEP European Integrated Project, combining clinical pharmacogenomic/pharmacogenetic studies on depressed patients with preclinical investigations on animal models. FSL and FRL rats were subjected to maternal separation and both stressed and control animals were split into groups receiving chronic escitalopram treatment or vehicle. Hippocampal protein expression was evaluated by 2Dgel electrophoresis and subsequent image analysis. Comparisons among groups were performed by univariate and multivariate statistical analysis to detect changes induced by the stress exposure and the pharmacological treatment, associated with a different genetic background. This study shows that different groups of proteins are modulated by stress in hippocampus of the FRL and FSL rats as well as by the antidepressant treatment in the two gene-environment backgrounds. Identified proteins are involved mainly in cellular primary metabolism and biosynthesis, in protein processing, cytoskeleton organization, and in the regulation of neurogenesis and CNS development, suggesting new molecular correlates of vulnerability to depression, and of response to antidepressants.