Gene-environment interactions in a rat model of depression. Maternal separation affects neurotensin in selected brain...

Although the etiology of major psychiatric disorders has not been elucidated, accumulating evidence indicates that both genetic and early environmental factors play a role. We have previously demonstrated behavioral and neurochemical changes both in non-manipulated genetic rat models of depression, such as Flinders Sensitive Line (FSL) and Fawn Hooded (FH), and in normal rats following maternal separation (MS). The aim of the present study was to extend this work by exploring whether neurotensin (NT), a peptide implicated in several psychiatric disorders, is altered in a new animal model based on gene - environment interactions. More specifically, we used the FSL rats as a genetic model of depression and the Flinders Resistant Line (FRL) as controls and subjected them to MS. Pups randomly assigned to the MS procedure were separated from the dam as a litter for 180min daily between postnatal day 2 to 14. On postnatal day 90, rats were weighed and sacrificed by a two second high energy focused microwave irradiation and several brain regions were obtained by micropuncture. Neurotensin-like immunoreactivity (NT-LI) was measured by radioimmunoassay (RIA). The results showed that the FSL rats compared to the FRL rats have higher baseline NT-LI concentrations in the temporal cortex and periaqueductal gray and a markedly different response to maternal separation. The only observed change following maternal separation in the FRL rats was an NT-LI increase in the periaqueductal gray. In contrast, in the FSL significant increases were found in the nucleus accumbens, hippocampus, and entorhinal cortex and a decrease was seen in the temporal cortex after MS. The present study revealed baseline regional differences in NT-LI concentrations between the FSL and FRL strains and demonstrated that early MD differentially affects the two strains. The relevance of these alterations for depression as well as possible mechanisms underlying this gene-environment interaction are discussed.