Attenuation of Chronic Administration of Mirtazapine on Neonatal Dexamethasone Treatment-Induced Depression-Like Behavior in Adult Rats

Abstract

Dexamethasone (DEX) is a synthetic glucocorticoid that is commonly administered to low birth weight preterm infants for preventing the development of respiratory distress syndrome (RDS). However, clinical studies have suggested potentially deleterious long-term effects of both neonatal glucocorticoid (GC) treatment and neonatal DEX treatment (NDT) in preterm infants on subsequent brain development, somatic growth and catabolic changes. In this study, we used experimental animal model to mimic the conditions in human patients. Briefly, animals subjected to subcutaneous injection of taped doses of DEX for a total of 3 days (from postnatal day 1 to 3, PN1-PN3). Rats were then examined by using forced swimming tests (FST), locomotor activity monitoring at the age of 8 weeks old. Our results indicated that NDT increases depression-like behavior after acute stress in adult rats. In addition, chronic administration of antidepressant mirtazapine (MIR) suppresses NDT-induced depression-like behavior in a dose-dependent manner (1, 5, 20, and 40 mg/kg), with maximal effect at 40 mg/kg. In conclusion, our results showed that NDT enhanced depression-like behavior following acute stress, which may enhance susceptibility for having depressive disorders in adulthood, after chronic administration of the antidepressant MIR, the depression-like behavior was significantly reduced in NDT rats.