Giorgia Boero

Maternal separation attenuates the effect of adolescent social isolation on HPA axis responsiveness in adult rats

Adverse early life experiences that occur during childhood and adolescence can have negative impacts on behavior later in life. The main goal of our work was to assess how the association between stressful experiences during neonatal and adolescent periods may influence stress responsiveness and brain plasticity in adult rats. Stressful experiences included maternal separation and social isolation at weaning. Three hours of separation from the pups (3-14 PND) significantly increased frequencies of maternal arched-back nursing and licking-grooming across the first two weeks postpartum. Separation also induced a long-lasting increase in dams blood levels of corticosterone. Maternal separation did not modify brain and plasma allopregnanolone and corticosterone levels in adult offspring, but they demonstrate partial recovery from the reduction induced by social isolation during adolescence. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were subjected to maternal separation was markedly reduced with respect to that observed in animals that were just socially isolated. All experimental groups showed a significant reduction of BDNF and Arc protein expression in the hippocampus. However, the reduction of BDNF observed in animals that were maternally separated and subjected to social isolation was less significantly pronounced than in animals that were just socially isolated. The results sustained the mismatch hypothesis stating that aversive experiences early in life trigger adaptive processes, thereby rendering an individual to be better adapted to aversive challenges later in life.

Juvenile social isolation affects maternal care in rats: involvement of allopregnanolone

RationaleSocial isolation of rats immediately after weaning is thought to represent an animal model of anxiety-like disorders. Socially isolated virgin females showed a significant decrease in allopregnanolone levels, associated with increased anxiety-related behavior compared with group-housed rats.ObjectivesThe present study investigates whether post-weaning social isolation affects maternal behavior and assesses neuroactive steroid levels in adult female rats during pregnancy and postpartum.ResultsSocially isolated dams displayed a reduction in the frequency of arched back nursing (ABN) behavior compared to group-housed dams. In addition, both total and active nursing were lower in socially isolated dams compared to group-housed dams. Compared to virgin females, pregnancy increases allopregnanolone levels in group-housed as well as isolated dams and such increase was greater in the latter group. Compared to pregnancy levels, allopregnanolone levels decreased after delivery and this decrease was more pronounced in isolated than group-housed dams. Moreover, the fluctuations in plasma corticosterone levels that occur in late pregnancy and during lactation follow a different pattern in socially isolated vs. group-housed rats.ConclusionsThe present results show that social isolation in female rats decreases maternal behavior; this effect is associated with lower allopregnanolone concentrations at postpartum, which may account, at least in part, for the poor maternal care observed in socially isolated dams. In support of this conclusion is the finding that finasteride-treated dams, which display a decrease in plasma allopregnanolone levels, also showed a marked reduction in maternal care, suggesting that allopregnanolone may contribute to the quality of maternal care.

Low doses of prenatal ethanol exposure and maternal separation alter HPA axis function and ethanol consumption in adult male rats

ABSTRACT Adverse maternal behaviors during pregnancy and unfavorable postnatal experiences during development are associated with an increased risk of developing psychiatric disorders, as well as, a vulnerability to alcohol addiction in adulthood. Here, we examined the effects of combined ethanol exposure during late pregnancy and postnatal maternal separation (MS) on HPA responsiveness, anxiety behavior and preference for alcohol consumption in adult male rats. Animals exposed to both conditions revealed a decrease in blood levels of allopregnanolone accompanied by increased anxiety behavior. In addition, basal blood levels of corticosterone were markedly decreased in all experimental groups while increases in the foot‐shock‐induced corticosterone levels were more pronounced in MS animals. Finally, evaluating EtOH drinking behavior, MS animals exhibited a remarkable EtOH preference even at low doses (0.1–1%). Altogether, these data suggest that adverse conditions, alone or in combination, may alter anxiety–like states as well as modify behavior towards alcohol consumption. HighlightsPerinatal stress affects anxiety and preference for alcohol intake in rats.Decrease in AP blood levels are accompanied with an increased anxiety behavior.Blood level of CTS were strongly decreased in rats exposed to perinatal stress.Foot‐shock‐induced CTS increase was more pronounced in MS animals.MS animals revealed a remarkable EtOH preference even at low doses (0.1–1%).

Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats

ABSTRACT We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid‐binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long‐lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group‐housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group‐housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2‐arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid‐mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post‐traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. HighlightsSocial isolation (SI) induced long‐lasting CRH, ACTH and CORT responses after acute stress.SI impairs MR and GR balance in the hippocampus and hypothalamus.SI alters GR expression and function.SI alters the hypothalamic endocannabinoid system.