Developmental fluoxetine and prenatal stress effects on serotonin, dopamine, and synaptophysin density in the PFC and hippocampus of offspring at weaning

Abstract

Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning.

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

“…However, when maternal behavior was assessed after perinatal administration of the SSRI paroxetine via drinking water in rats, there were minimal effects of drug treatment on maternal activities like grooming and nursing (Glover et al, 2015). It is important to note that ADs can impact neuroendocrine signaling; hormonal alterations can affect neurotrophic factors and monoamines in pregnant rats that may influence offspring in utero (Bagdy, 1996;Delarue et al, 2001;Fuller, 1996;Gemmel et al, 2016;Morrison et al, 2004;Rayen et al, 2015Rayen et al, , 2013. Moreover, it is possible that pups experienced drug withdrawal after treatment stopped on P21, resulting in effects similar to those observed in human infants with neonatal abstinence syndrome (Forsberg et al, 2014;Klinger et al, 2011;Levinson-Castiel et al, 2006), but such potential effects were not measured in the pups.…”

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

“…Thus, maternal postpartum FLX can impact development of female endocrine physiology which could alter hippocampal plasticity. It should be noted that different studies using a lower dose of FLX (5 mg/kg; s.c.) in dams found that maternal postpartum FLX has no effect on density of DCX-expressing cells in males or females at weaning [56], in adolescence [17], or in adulthood ([58]; only males examined). This suggests that only higher doses of FLX alter density of DCX-expressing cells in pre-adolescent offspring.…”

The Neurobiology of Postpartum Anxiety and Depression

“…Research in the hippocampus (a brain area that has received the most attention in animal models of PPD due to its relationship with depression and high degree of plasticity in adulthood) shows alterations in its neurogenesis and dendritic plasticity after stress in the peripartum period [54, 55,57,61]. In line with clinical work, animal models are also pointing to pivotal roles for central serotoninergic system and the hypothalamic-pituitary-adrenal system in postpartum depression [62,63], although much more research is needed in this area.…”