Florent Pittet

Effects of Chronic Social Stress and Maternal Intranasal Oxytocin and Vasopressin on Offspring Interferon-γ and Behavior.

Recent studies support the hypothesis that the adverse effects of early-life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioral programing effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS)-exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress-induced deficits in offspring anxiety and social behavior and that these effects would be associated with changes in interferon-γ (IFNγ). Control and CSS-exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFNγ and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFNγ levels and exhibited increased repetitive/perseverative and anxiety behaviors and deficits in social behavior. These effects were modulated by AVP and OXT in a context- and behavior-dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviors and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFNγ levels were elevated in the F2 offspring of OXT-treated F1 dams, but IFNγ was not correlated with the behavioral effects. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviors in the female offspring of early-life social stress-exposed dams. Both maternal AVP and OXT are effective at preventing social stress-induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. OXT is specifically effective at preventing repetitive/perseverative behaviors, yet is ineffective at preventing deficits in overall social behavior.

Intergenerational accumulation of impairments in maternal behavior following postnatal social stress

Early adversity such as depressed maternal care can have long-term physiological and behavioral effects on offspring and future generations. Exposure to chronic social stress (CSS), an ethologically model of postpartum depression and anxiety, during lactation impairs maternal care and exerts similar effects on the F1 dam offspring of the stressed F0 dams. These changes associate with increased corticosterone and neuroendocrine alterations. CSS F2 offspring further display decreased social behavior as juveniles and adults and decreased basal levels of corticosterone. This current study investigates the intergenerational inheritance of alterations in maternal behavior in F2 CSS dams together with neuroendocrine and immune markers to explore whether aspects of maternal behavior are intergenerationally inherited through immune and neuroendocrine mechanisms. We find that defects in maternal care behavior persist into the F2 generation with F2 dams exhibiting a pervasively depressed maternal care and increased restlessness throughout lactation. This occurs together with reduced basal cortisol (in contrast to an increase in F1 dams), a lack of changes in neuroendocrine gene expression, and reduced serum ICAM-1 (intercellular adhesion molecule-1) levels - a marker for inflammation and blood–brain barrier integrity. The data support the hypothesis that the effects of chronic social stress can accumulate across multiple generations to depress maternal care, increase restlessness and alter basal functioning of the immune system and hypothalamic pituitary adrenal axis.

Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development

We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

Brain Reward Pathway Dysfunction in Maternal Depression and Addiction: A Present and Future Transgenerational Risk

Two research areas that could benefit from a greater focus on the role of the reward pathway are maternal depression and maternal addiction. Both depression and addiction in mothers are mediated by deficiencies in the reward pathway and represent substantial risks to the health of offspring and future generations. This targeted review discusses maternal reward deficits in depressed and addicted mothers, neural, genetic, and epigenetic mechanisms, and the transgenerational transmission of these deficits from mother to offspring. Postpartum depression and drug use disorders may entail alterations in the reward pathway, particularly in striatal and prefrontal areas, which may affect maternal attachment to offspring and heighten the risk of transgenerational effects on the oxytocin and dopamine systems. Alterations may involve neural circuitry changes, genetic factors that impact monoaminergic neurotransmission, as well as growth factors such as BDNF and stress-associated signaling in the brain. Improved maternal reward-based preventative measures and treatments may be specifically effective for mothers and their offspring suffering from depression and/or addiction.

Contributions of family social structure to the development of ultrasociality in humans.

The evolution of ultrasociality in humans may have involved the evolutionarily significant mechanisms that govern family social structure in many animal species. Adverse effects of ultrasociality in humans may be mediated by maladaptive effects of modern civilization on family groups, as many of the effects on both families and societies are especially severe in dense populations made possible by agriculture.

Transgenerational effect of maternal deprivation in Japanese Quail

In horses, the use of a positive reinforcement as a food reward has been shown to enhance learning performances and to promote a positive relation to the trainer. Here, we investigated whether grooming at the whither, known to induce a decrease in the groomee’s heart rate, could be used as a primary reinforcement, by comparing it to a food reward. Twenty Konik horses (9 females, 11 males), aged 1-2 years, with no previous learning experience and no contact with humans, except for feeding, were trained to remain immobile in response to a vocal command. Training was performed 5 minutes per day for 6 days. Horses were allocated to one of two training groups: in the food-reward group (FR: n=10), the trainer hand-gave a piece of carrot to the horse after it responded correctly, while in the grooming-group (GR: n=10), the trainer scratched the horse’s wither. Duration of immobility and trainer-directed behaviours were continuously recorded. The results indicate that: (1) using food rewards facilitated learning (duration of immobility: P<0.05), whereas grooming rewards led to lower performances; (2) the type of reward has a clear effect on the horse’s attentional state during training. While no difference between both groups were scored in the first days of training, on the last day the FR group spent more time monitoring (i.e. head rotations towards the trainer), more time gazing at and expressed more investigative behaviours towards the trainer (e.g. sniffing) than the GR group (MW, P<0.05 in all cases). In conclusion, these results suggest that the use of a food reward is associated with an increase of motivation, leading to a better efficiency in promoting learning that may well have been mediated by attentional factors, while alternative such as scratching (usually use in training techniques) appears less efficient.In mammals and birds, a maternal deprivation in early life, which is common in intensive livestock, strongly influences behavioural development of young animals, for short and long terms. Maternal deprivation also seems to affect the development of the next generation in mammals. Because such effects are rarely studied in birds, we analyzed the transgenerational effect of maternal deprivation in Japanese quail. First, we determined the behavioural characteristics of females hatched from eggs laid by mothered females (M females) and non-mothered females (NM) (emotional and social characteristics, cognitive abilities in a spatial task, maternal behaviour). Then, we followed the behavioural development of young brooded by those females (4 chicks per female). We used Mann-Whitney non-parametric tests to compare the two sets of females. M (n=22) and NM (n=22) females presented behavioural differences in adulthood, particularly regarding global activity. Indeed, NM females were less active (number of steps in openfield test: M=78.6±17.9, NM=32.0±8.5, P=0.009). Then, NM females showed a higher social motivation than M females (conspecific approach latency: M=122.6±9.5 s, NM=94.5±12.5 s, P=0.022). Moreover, they showed lower cognitive abilities in a detour test (success rate: M=77.3%, NM=22.7%, P=0.006). Maternal behaviour of M and NM females seemed similar, although chicks brooded by NM females maintained greater distance from their mother at the end of the mothering period. Finally, chicks brooded by M and NM mothers were not different after emancipation. We showed here that an early maternal deprivation has an impact on behavioural characteristics of genetic daughters from these non-mothered females, in spite of few impacts on their maternal behaviour. Our study highlighted for the first time a transgenerational effect of such a deprivation in birds