Inherited behaviors, BDNF expression and response to treatment in a novel multifactorial rat model for depression

Background:

Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role.

Objective:

This study used, for the first time, a multifactorial selective breeding procedure to generate a distinct ‘depressed’ rat line (DRL).

Method:

The selection of the rat line was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined.

Results:

Decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited andnot necessarily triggered by salient chronic stress.

Conclusions:

This study provides a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease.

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