Stress Resilience is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm

The synaptogenic hypothesis of major depressive disorder implies that preventing the onset depressive-like behavior also prevents loss hippocampal spine synapses. By applying psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking development helpless by promoting stress resilience in rat learned helplessness paradigm is associated with a synaptoprotective action hippocampus. Adult ovariectomized intact female Sprague-Dawley rats (n = 297) were treated either diazepam, or vehicle, exposed to inescapable footshocks sham stress, tested an active escape task assess behavior. Escape-evoked corticosterone secretion, as well remodeling synapses at timepoint representing testing analyzed. In females, treatment prior exposure prevented behavior, blocked synapses, muted surge evoked testing. Although fluoxetine stimulated performance synaptogenesis under non-stressed conditions, almost all responses abolished following stress. Only much higher dose was capable partly reproducing strong protective actions diazepam. Importantly, these retained presence ovarian hormones. Our findings indicate preservation hippocampus, raising possibility that, besides synaptogenesis, synaptoprotection implicated antidepressant therapy.