Effects of maternal separation on neuropeptide Y and calcitonin gene-related peptide in "depressed" Flinders Sensitive Line rats: a study of gene-environment interactions.

Interactions between genetic vulnerability to stress/depression and early life experience may play a crucial role in the pathogenesis of mood disorders. Here we explore this hypothesis by superimposing early life trauma in the form of maternal deprivation for 180 min per day from postnatal day 2 to 14 onto a genetic model of depression/susceptibility to depression, Flinders Sensitive Line (FSL) and their controls, Flinders Resistant Line (FRL) rats. We investigate effects on neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) like immunoreactivity (LI) in 10 brain regions as these neuropeptides are affected by antidepressants and are altered in cerebrospinal fluid of depressed patients. NPY-LI was reduced while CGRP-LI was elevated in hippocampus and frontal cortex of "genetically depressed" FSL rats. The two peptides displayed a significant negative correlation in these regions that was strongest in the FSL strain. Maternal deprivation exacerbated the strain difference in hippocampal CGRP-LI, while it was without effect on NPY-LI. FSL rats had higher tissue concentration of both neuropeptides in periaqueductal grey and higher NPY-LI in caudate/putamen. Maternal deprivation selectively raised CGRP-LI in amygdala of the FRL control stain. Thus, in two brain regions implicated in the neurobiology of depression, hippocampus and frontal cortex, changes in CGRP-LI and NPY-LI were in opposite direction, and CGRP-LI appears to be more responsive to adverse experience. Our findings thus support the hypothesis that genetic disposition and developmental stress may contribute to the susceptibility to depression by exerting selective neuropeptide- and brain region-specific effects on adult neurobiology.