Abstract
ObjectiveIn this study, the effect of maternal deprivation (MD) and chronic unpredictable stress (CUS) in inducing depressive behaviors and associated molecular mechanism were investigated in rats.MethodsMaternal deprivation was established by separating pups from their mothers for 6 hours daily from postnatal day 1 to day 14. Chronic unpredictable stress was established by water deprivation, elevated open platform, food deprivation, restraint stress and electric foot shock. The depressive behaviors were determined by use of sucrose preference test and forced swim test.ResultsRats in MD/CUS group exhibited lower sucrose preference rate, longer immobility time, and lighter body weights than rats in other groups (MD/control, non-MD/CUS and non-MD/control group). Meanwhile, higher miR-504 expression and lower dopamine receptor D1 (DRD1) and D2 (DRD2) expression were observed in the nucleus accumbens of rats in the MD/CUS group than in the other three groups. MiR-504 expression correlated negatively with DRD1 gene expression and sucrose preference rate in the sucrose preference test, but correlated positively with immobility time in forced swim test. Both DRD2 mRNA and protein expression correlated negatively with immobility time in forced swim test.ConclusionThese results suggest that MD enhances behavioral vulnerability to stress during adulthood, which is associated with the upregulation of miR-504 and downregulation of DRD2 expression in the nucleus accumbens.
Highlights
Early-life stress is one of the most important adverse events associated with an increased risk of developing depression and anxiety disorders [1,2]
We investigated miR-504 and dopamine receptor D1/D2 expression in the nucleus accumbens (NAc) of rats that experienced maternal deprivation (MD) and chronic unpredictable stress (CUS) as well as behavioral consequences of early life MD on CUS exposure during adulthood
The sucrose preference rate was significantly lower in MD rats than in non-MD rats (p,0.05)
Summary
Early-life stress is one of the most important adverse events associated with an increased risk of developing depression and anxiety disorders [1,2]. Individuals exposed to adverse events during early life are more prone to developing depression-like behavior upon exposure to stress in adulthood [3,4]. A large number of preclinical studies in animal models and clinical studies have consistently revealed that adverse experiences in early life can affect long-term behavior and function of the neurotransmission system during adult life [5,6]. One of the established animal models for analyzing the influence of early life adversity is maternal deprivation in rats, which is important for regulating the development of the neurotransmission system as well as brain functions and emotional behaviors during adulthood [7,8]. We hypothesize that the dysfunction of the neurotransmission system induced by maternal deprivation may increase behavioral vulnerability to stress in adults
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