Treadmill exercise alleviated prenatal buprenorphine exposure-induced depression in rats

Abstract

Mounting evidence suggests that physical exercise shows health benefits in a range of diseases, including psychiatric disorders. Perinatal opioid exposure produces neurobehavioral abnormality, which includes depression symptoms, in patients and their offspring following chronic use of buprenorphine, a mixed agonist/antagonist with a high affinity to opioid receptors, for pain control. Previously, we demonstrated that prenatal buprenorphine exposure in pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days caused the development of depression-like phenotypes in pups at postnatal day 21. Using the same prenatal buprenorphine exposure model, we further demonstrated that a 4-week course of moderate treadmill exercise conducted on pups starting from postnatal day 22 improved depression-like neurobehaviors. Prenatal buprenorphine exposure-induced neurobehavioral changes were accompanied by reductions of neuronal survival, neural stem cell-associated genes, plasma level of brain-derived neurotrophic factor (BDNF) and serotonin, phosphorylated tropomyosin-related kinase receptor type B (TrkB), phosphorylated extracellular signal-regulated kinase (ERK), PKA activity, phosphorylated cAMP response element-binding protein (CREB), and CREB DNA binding activity, as well as elevation of repressor element-1 silencing transcription factor (REST), oxidative stress, and inflammatory responses. Those changes in parameters of plasma and brain were improved by treadmill exercise. In conclusion, the findings of the current study suggest that a non-pharmacological option, i.e., moderate treadmill exercise, alleviated the development of depression-like neurobehaviors by resolving the oxidative and inflammatory burden as well as by enhancing neurochemical and neuroendocrine signaling.