Environmental enrichment affects behavioral and pharmacological response to antidepressants in CF1 mice

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.