Abstract
Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child’s neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg/kg/day) or vehicle during pregnancy and lactation followed by analysis of offspring’s behavior at juvenile and adolescent age. We found mirtazapine induced significant alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males (p≤0.05) and increased their active behavior in forced swim test (p≤0.01). Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile (p≤0.05) and adolescent (p≤0.05) females and impairment of spatial memory (p≤0.01) in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced significant alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and/or chronic pregestational stress.
Highlights
An estimation of 17% men and 25% women experience an episode of major depressive disorder (MDD) at least once in their life [1]
Testosterone levels rise and become the most important hormone associated with negative mood, with a high correlation index, suggesting its severe role in the etiology of post-partum depression [9], while higher levels of DHEA during pregnancy were associated with better mood but after delivery its decline was related to mood aggravation
We evaluated the spontaneous pain of the mothers by the Rat Grimace Scale (RGS) and we found increased facial expression indicating pain in those mothers, which were exposed to stress schedule
Summary
An estimation of 17% men and 25% women experience an episode of major depressive disorder (MDD) at least once in their life [1]. Testosterone levels rise and become the most important hormone associated with negative mood, with a high correlation index, suggesting its severe role in the etiology of post-partum depression [9], while higher levels of DHEA during pregnancy were associated with better mood but after delivery its decline was related to mood aggravation. It is not the effect of solely one of them but the combined action of different hormones and neurotransmitters at different time points that induce mood alterations
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