Approximately 60% of Major Depressive Disorder (MDD) patients do not respond to FDA-approved antidepressants. Introducing effective pharmacotherapies for this treatment-resistant population is hindered by the lack of pre-clinical screening assays that accurately model the clinical features of TRD. The purpose of this research was to screen representatives of different classes FDA-approved antidepressants and one novel antidepressant in two genetic lines of domestic fowl chicks that have previously been identified as stress-vulnerable and stress-resilient in the chick anxiety depression model. Separate groups of socially raised Black Australorp (stress-vulnerable) and Production Red (stress-resilient) chicks were administered the tricyclic antidepressant imipramine (0-20 mg/kg), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (0-10 mg/kg), the tetracyclic antidepressant maprotiline (0-10 mg/kg), the glutamate receptor antagonist ketamine (0-15 mg/kg), or vehicle (physiological saline) and placed individually inside sound attenuating chambers for a 90-minute test period. The behavioral measure of distress vocalizations (DVocs) was recorded via custom designed software. Replication and validation of previous findings of stress sensitivity in the two genetic lines was measured by calculation of the onset of behavioral despair during the depression like phase (30-90 min). Verifying previous research, Black Australorps entered behavioral despair approximately 25% faster than Production Reds signifying the stress-vulnerability of the Black Australorp line. In the depression-like phase, Black Australorps were insensitive to imipramine and fluoxetine, but sensitive to ketamine, a finding that parallels the clinical picture of TRD.

Utilization of the Black Australorps genetic line in the chick anxiety-depression model may be a novel and lone preclinical screening to identify alternative mechanisms and promising leads for TRD.