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Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Individuals are increasingly exposed to light at night. Exposure to constant light (LL) disrupts circadian rhythms of locomotor activity, body temperature, hormones, and the sleep-wake cycle in animals. Other behavioural responses to LL have been reported, but are inconsistent. The present experiment sought to determine whether LL produces changes in affective responses and whether behavioural changes are mediated by alterations in glucocorticoid concentrations. Relative to conspecifics maintained in a light/dark cycle (LD, 16:8 light/dark), male Swiss-Webster mice exposed to LL for three weeks increased depressive-like behavioural responses as evaluated by the forced swim test and sucrose anhedonia. Furthermore, providing a light escape tube reversed the effects of LL in the forced swim test. LL mice displayed reduced anxiety as evaluated by the open field and elevated-plus maze. Glucocorticoid concentrations were reduced in the LL group suggesting that the affective behavioural responses to LL are not the result of elevated corticosterone. Additionally, mice housed in LD with a clear tube displayed increased paired testes mass as compared to LL mice. Taken together, these data provide evidence that exposure to unnatural lighting can induce significant changes in affect, increasing depressive-like and decreasing anxiety-like responses.

This study investigated the effect of maternal pinealectomy and postnatal pinealectomy on affective responses. Siberian hamsters were born to either pinealectomized or sham-operated dams and then underwent pinealectomy or a sham operation. Maternal pinealectomy increased depressive-like responses of offspring in the forced swim test. Maternal pinealectomy increased rearing behaviour and postnatal pinealectomy increased locomotor behaviour in the open field test. These results suggest that prenatal melatonin organizes adult affective responses.

Many psychological disorders are characterized by anxiety and alterations in social interactions. Recent studies demonstrate that the chemical messenger nitric oxide (NO) can regulate both anxiety and social behaviours. We tested whether an enzyme that produces NO in the brain, neuronal nitric oxide synthase (nNOS), serves as an interface between social interactions and anxiety-like behaviour. Several investigators have observed that mice increase anxiety-like responses in the elevated plus-maze after pair housing. nNOS gene deletion and 3-Bromo-7-Nitroindazole were used to inhibit the production of neuronal NO. Similar to previous studies, pair housing reduced open arm exploration in the elevated plus-maze. Pair housing also increased corticotropin-releasing hormone (CRH) immunoreactive cells in the paraventricular nucleus (PVN) of the hypothalamus. Inhibition of NO production increased open arm exploration in pair-housed mice but decreased open arm exploration in individually housed mice. These results suggest that the effect of nNOS inhibition on anxiety-like responses is context dependent and that behavioural responses to social housing are altered after nNOS inhibition. This research suggests that NO may play an important role in mediating the effect social interactions have on anxiety.

Abstract: Challenging early life events can dramatically affect mental health and wellbeing. Childhood trauma and neglect can increase the risk for developing depressive, anxiety, and substance abuse disorders. Early maternal separation in rodents has been extensively studied and induces long-lasting alterations in affective and stress responses. However, other developmental periods (e.g., the pubertal period) comprise a critical window whereby social and environmental complexity can exert lasting changes on the brain and behavior. In this study, we tested whether early life environmental complexity impacts affective responses, aggressive behaviors, and expression of neuronal nitric oxide synthase (nNOS), the synthetic enzyme for nitric oxide, in adulthood. Mice were weaned into social+nonsocial enrichment, social only enrichment, or standard (isolated) laboratory environments and were tested in open field, elevated plus maze, forced swim, and resident–intruder aggression tests 60days later. Social+nonsocial enrichment reduced locomotor behavior and anxiety-like responses in the open field and reduced depressive-like responses in the forced swim test. Social housing increased open arm exploration in the elevated plus maze. Both social+nonsocial enrichment and social housing only reduced aggressive behaviors compared with isolation. Social+nonsocial enrichment also increased body mass gain throughout the study. Finally, socially-housed mice had reduced corticosterone concentrations compared with social+nonsocial-enriched mice. Behavioral testing reduced nNOS-positive neurons in the basolateral amygdala and the ventral lateral septum, but not in the social+nonsocial-enriched mice, suggesting that environmental complexity may buffer the brain against some environmental perturbations. [Copyright &y& Elsevier]

Abstract: Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, l-arginine, has been understudied in regard to behavioral regulation. l-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain l-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an l-arginine-depleted, l-arginine-supplemented, or standard level of l-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. l-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. [Copyright &y& Elsevier]