Melatonin modulates catecholamine biosynthesis and re-uptake in adrenal medulla of rats exposed to chronic unpredictable mild stress

Abstract

Introduction: Stress is considered a determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. Many studies have assessed the antidepressant-like activity of the melatonin, a neurohormone synthesized in the pineal gland. Thus, in the present study, we examined the effect of chronic melatonin treatment on mRNA levels and protein content of catecholamines biosynthetic enzymes (TH, DBH and PNMT) and transporters (NET, VMAT2) in adrenal medulla of rats exposed to chronic unpredictable mild stress (CUMS). Material and Methods: CUMS was used as an animal model of depression. Exposure of rats to CUMS and placebo or melatonin (10 mg/kg body weight, i.p.) administration started on the same day and was continued for 4 weeks. For quantifying TH, DBH, PNMT, NET and VMAT2 mRNA and protein levels we used realtime PCR and Western blot analysis. Results: We observed that CUMS induced increased mRNA levels of catecholamine biosynthetic enzymes (TH, DBH, and PNMT), and noradrenaline transporter NET, while treatment with melatonin decreased these biosynthetic enzymes and transporter. Conversely, CUMS induced a decrease in protein content of TH and NET, while chronic melatonin treatment increased NET protein levels in both control and stressed rats. CUMS and melatonin treatment has no effect on mRNA levels and protein content of VMAT2. Conclusion: This study suggests that the observed decrease of catecholamine biosynthesis and enhanced re-uptake in adrenal medulla of rats exposed to CUMS are connected to the beneficial effects of chronic melatonin treatment