Sex-dependent behavior, neuropeptide profile and antidepressant response in rat model of depression

•FSL rats weighed significantly less than SD rats.•Female FSL rats showed the most pronounced depressive-like phenotype and response to escitalopram treatment.•The behavioural findings were not paralleled by changes in measures of NPY, CRH and CGRP. A plethora of animal models of depression is described in the literature, aiming at mimicking different aspects of depression. Understanding the link between depression and stress has been and remains a major focus area for development of animal models, but lines of research with a more mechanistic focus targeting deficiencies in neurotransmitter systems or dysfunctional neuronal circuitries and neuroinflammation are also pursued vigorously. The main objectives of the present study were systematically to evaluate strain and sex characteristics of a genetic animal model, the Flinders Sensitive Line (FSL)/ Flinders Resistant Line (FRL), by applying behavioral, molecular and pharmacological measures relevant to depression, and compare it with the outbred Sprague Dawley rat. In addition, we aimed at comparing across strains and sex the expression of NPY, CRF, CGRP in brain regions critically involved in mood regulation, and investigating the responses to escitalopram. In line with the comparisons of FSL and FRL rats, the FSL rats weighed significantly less than SD rats. Overall, escitalopram treatment for 5–6 weeks did not have a major impact on weight, but displayed a significant antidepressant-like effect, however without any changes in NPY, CRH and CGRP expression. Our comparative study of FSL and SD rat with respect to behavioral characteristic, neuropeptide levels in various brain regions (protein and mRNA levels), and response to long-term antidepressant treatment revealed that female FSL rats showed the most pronounced depressive-like phenotype and response to SSRI treatment. However, these findings were not paralleled by changes in measures of NPY, CRH and CGRP function.