Differential impact of stress and environmental enrichment on corticolimbic circuits

Stress exposure can produce profound changes in physiology and behavior that can impair health and well-being. Of note, stress exposure is linked to anxiety disorders and depression in humans. The widespread impact of these disorders warrants investigation into treatments to mitigate the harmful effects of stress. Pharmacological treatments fail to help many with these disorders, so recent work has focused on non-pharmacological alternatives. One of the most promising of these alternatives is environmental enrichment (EE). In rodents, EE includes social, physical, and cognitive stimulation for the animal, in the form of larger cages, running wheels, and toys. EE successfully reduces the maladaptive effects of various stressors, both as treatment and prophylaxis. While we know that EE can have beneficial effects under stress conditions, the morphological and molecular mechanisms underlying these behavioral effects are still not well understood. EE is known to alter neurogenesis, dendrite development, and expression of neurotrophic growth factors, effects that vary by type of enrichment, age, and sex. To add to this complexity, EE has differential effects in different brain regions. Understanding how EE exerts its protective effects on morphological and molecular levels could hold the key to developing more targeted pharmacological treatments. In this review, we summarize the literature on the morphological and molecular consequences of EE and stress in key emotional regulatory pathways in the brain, the hippocampus, prefrontal cortex, and amygdala. The similarities and differences among these regions provide some insight into stress-EE interaction that may be exploited in future efforts toward prevention of, and intervention in, stress-related diseases.