Prenatal Stress Produces Social Behavior Deficits and Alters the Number of Oxytocin and Vasopressin Neurons in Adult Rats

Abstract

The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin (VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

“…While several studies indicated that oxytocin receptor expression and OXTR binding is elevated in several brain areas during parturition and breastfeeding and linked to reduced anxiety and depression in the mother (Lonstein et al, 2014), oxytocin signaling in offspring is less well studied. Intriguingly, rodent studies suggest that exposure to prenatal and postnatal maternal stress decreased the number of oxytocin positive cells in adult offspring as compared with offspring from non-stress exposed mothers (de Souza et al, 2013). Furthermore, prairie vole neonates injected with oxytocin display higher parental behavior, facilitated partner bonding and decreased corticosterone after a swim test later in life, as compared to animals injected with an oxytocin antagonist (Carter, 2003).…”

“…For instance, prenatally stressed adult male rats raised by their stress-exposed mothers not only showed impairment in social interactions but also a reduced number of oxytocin-positive neurons in the paraventricular nucleus as compared to adult male offspring born and raised by non-stressed mothers (de Souza et al, 2013). Additionally, elevated activity of the oxytocinergic system is also implicated in a dampening of the stress response by interacting with the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (Light et al, 2000;Neumann, 2002;Lee et al, 2009;Grewen and Light, 2011).…”

Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats

“…PRS might have caused an oxytocinergic hypotonus (Lee et al, 2007;de Souza et al, 2013), with an ensuing up-regulation of oxytocin receptors in target regions of hypothalamic oxytocinergic neurons, i.e., the hippocampus and amygdala. Carbetocin treatment reduced oxytocin receptor mRNA levels in the amygdala and hippocampus of PRS rats, and in the amygdala of unstressed rats.…”

Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives

“…For example, male rats born to mothers who experienced four sessions of restraint per day during the latter stages of pregnancy, exhibit reduced social interactions when repeatedly faced with a single conspecific in a familiar arena in adulthood (88). Interestingly this result was found as part of a social memory test, designed to determine if individuals could recognise a novel conspecific after habituation to a previous one.…”

“…Both pre-natal and juvenile stressors have been shown to significantly alter nonapeptide production in later life (88,(101)(102)(103)(104)(105). Maternal separation of mouse pups for three hours a day in the first two weeks of life causes opposite effects on the two main nonapeptides within the hypothalamus in adulthood; AVP was seen to be significantly upregulated, whereas OT was downregulated (106).…”