Running from depression: the antidepressant-like potential of prenatal and pre-pubertal exercise in adolescent FSL rats exposed to an early-life stressor.

OBJECTIVE: We aimed to answer the questions of whether early-life (perinatal and/or juvenile) exercise can induce antidepressant-like effects in a validated rodent model of depression, and whether such early-life intervention could prevent or reverse the adverse effects of early-life stress in their offspring. METHODS: Male and female Flinders sensitive line rats born to a dam that exercised during gestation, or not, were either maternally separated between PND02 and 16 and weaned on PND17 or not. Half of these animals then underwent a fourteen-day low-intensity exercise regimen from PND22. Baseline depressive-like behaviour was assessed on PND21 and then reassessed on PND36, whereafter hippocampal monoamine levels, redox state markers and metabolic markers relevant to mitochondrial function were measured. RESULTS: Pre-pubertal exercise was identified as the largest contributing factor to the observed effects, where it decreased immobility time in the FST by 6%, increased time spent in the open arms of the EPM by 9%. Hippocampal serotonin and norepinephrine levels were also increased by 35% and 26%, respectively, whilst nicotinic acid was significantly decreased. CONCLUSION: These findings suggest that pre-pubertal low-intensity exercise induces beneficial biological alterations that could translate into antidepressant behaviour in genetically susceptible individuals.

Genetically predisposed and resilient animal models of depression reveal divergent responses to early-life adversity.

OBJECTIVE: Early-life adversity (ELA) is one of the strongest predictors of childhood depression that may be exacerbated by a genetic predisposition to develop depression. We therefore investigated the bio-behavioural effects of an early-life stressor in an accepted rodent model of depression. METHODS: The Flinders sensitive line (FSL) and resistant line (FRL) rats were subjected to an early-life stressor, whereafter their bio-behavioural response during pubertal onset was evaluated. Male and female pups were maternally separated for 3 h per day from postnatal day 02 (PND02) to 17, when they were also weaned. Control animals were left undisturbed, until weaning on PND21. Depressive-like behaviour was analysed on PND21 and reassessed on PND36. Hippocampal monoamine levels, markers of oxidative stress and metabolic markers implicating mitochondrial function were also measured. RESULTS: On PND21, the non-maternal separation and early weaning (non-MSEW) FSL rats spent 10% more time mobile than their FRL controls in the tail suspension test (TST) yet displayed increased depressive-like behaviour in the forced swim test (FST) on PND36. This depressive-like behaviour coincided with increased hippocampal norepinephrine levels, serotonin turnover and a dysfunctional redox state. Maternal separation and early weaning (MSEW) appeared to initially reduce early-life (PND21) depressive-like behaviour in the TST but then induced depressive-like behaviour on PND36 and increased norepinephrine levels more profoundly in the FRL rats. CONCLUSION: These findings highlight the need to further investigate the stress response pathway in these animals and that the absence or presence of genetic susceptibility may influence the presentation of ELA effects.