Synbiotic diet produces antidepressant-like effects but alters ketamine activity in an avian model of treatment-resistant depression.

Pre- and probiotics promote a diverse and functional gut microbiota and have demonstrated both anxiolytic and antidepressant effects; however, how synbiotic diet interacts with antidepressant medications has not been fully investigated. This study sought to evaluate the potential anxiolytic or antidepressant effects of a synbiotic diet in an avian model that presents homologies with treatment-resistant depression. In addition, we sought to evaluate the potential interaction of a synbiotic diet combined with select doses of ketamine. Socially raised Black Australorp chicks were given either standard or synbiotic feed for 7 days. At 7 days posthatch, chicks from each feed condition were administered either 0, 5, or 10 mg/kg/ml ketamine 15 min before a 90-min isolation stressor, which elicits distress vocalizations (DVocs) that temporally represent a panic-like phase followed by a depression-like phase. Saline-treated chicks given the synbiotic diet displayed significantly higher DVoc rates in the depression-like phase compared with saline-treated animals in the standard feed condition, indicative of attenuation of behavioral despair [F(1,22) = 5.45, P < 0.05]. Similarly, in the standard diet condition, ketamine 10 mg/kg produced elevated DVoc rates; however, under the synbiotic diet, both doses of ketamine produced a suppression of DVoc rates in the depression-like phase. These findings suggest that a synbiotic diet produces antidepressant-like effects in the model and a possible negative interaction between synbiotics and ketamine. While preliminary, the findings suggest the concurrent use of pre- and probiotic supplements and ketamine may produce contradictory effects and warrant further investigation.