Quicker Antidepressant Results with Environmental Enrichment

From an article published in June 2023 in Translational Psychiatry

Coutens, B., Lejards, C., Bouisset, G. et al. Enriched environmental exposure reduces the onset of action of the serotonin norepinephrin reuptake inhibitor venlafaxine through its effect on parvalbumin interneurons plasticity in mice. Transl Psychiatry 13, 227 (2023). https://doi.org/10.1038/s41398-023-02519-x

Depression is a complex mental disorder characterized by emotional and cognitive symptoms. While antidepressant medications are commonly prescribed, their effects can take weeks to manifest fully. In this study, researchers investigated the potential of combining the antidepressant venlafaxine with environmental enrichment (EE) to accelerate the onset of its therapeutic effects.

The study

In the study, they used an experimental model of depression in mice. These “depressed displayed a depressive-like phenotype characterized by anxiety, resignation, impairments in self-care, spatial memory, and social recognition.

Mice were split into 2 groups and 2 subgroups:

1. a standard housing group
   • administered placebo, or
   • administered antidepressant (venlafaxine)
2. an environmental enrichment group
   • administered placebo, or
   • administered antidepressant (venlafaxine)

At 2 weeks and 8 weeks, they ran a battery of cognitive and emotional tests on the animals. They also sacrificed some of the animals after 2 weeks to compare their brains with those who did the experiment for 8 weeks.

Results

1. After 2 weeks:
   • In standard housing conditions
     • With the antidepressant: No improvements
   • In Environmental Enrichment conditions:
     • With the antidepressant: both the emotional and cognitive symptoms of depression decreased significantly
     • Without the antidepressant: only the cognitive symptoms improved
2. After 8 weeks:
   • In standard housing conditions: both cognitive and emotional functions were fully restored
   • In Environmental Enrichment conditions:
     • With the antidepressant: both cognitive and emotional functions were fully restored
     • Without the antidepressant: both cognitive and emotional functions were fully restored

Furthermore, the study investigated the role of the extracellular matrix, specifically the perineuronal nets (PNNs) surrounding hippocampal interneurons, in the delayed onset of antidepressant action. Inhibiting the degradation of PNNs using doxycycline prevented the behavioral recovery in depressed mice treated with venlafaxine and exposed to EE. Similarly, pharmacological degradation of hippocampal PNNs replicated the rapid antidepressant effects of the venlafaxine-EE combination.

Discussion

The findings of this study highlight the potential of combining antidepressants with environmental enrichment to accelerate the medication’s effects.

These results shed light on the importance of environmental factors and neuroplasticity in the treatment of depression. Further research is needed to elucidate the precise mechanisms underlying the interaction between venlafaxine, environmental enrichment, and the extracellular matrix in promoting rapid antidepressant effects.