Foster litters prevent hypothalamic-pituitary-adrenal axis sensitization mediated by neonatal maternal separation.

Neonatal maternal separation of rat pups has been shown to produce long-term increases in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, elevated levels of hypothalamic corticotropin releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN), and enhanced anxiety-like behavior. These effects appear to be at least partially mediated by subtle disruptions in the quality of maternal-pup interactions. This hypothesis was tested by providing half the dams with foster litters during the maternal separation paradigm, so that in those litters, only the pups and not the dams were experiencing a period of separation. The separation protocol took place daily from PND2-14 for either 15 min (HMS15, handled) or 180 min (HMS180, maternal separation). During the period of separation dams were either transferred to adjacent cages without any pups present (HMS15, HMS180) or to cages containing an age-matched foster litter (HMS15F, HMS180F). As adults, the HMS180 progeny exhibited the expected increased expression of CRF mRNA in the PVN, stress hyper-responsiveness to airpuff startle and evidence of impaired feedback both in the CORT response, as well as in response to the dexamethasone suppression test. The HMS180F rats, however, appeared to be resistant to these effects of maternal separation as they demonstrated CRF mRNA levels intermediate between HMS15 and HMS180 rats. Their stress responses and feedback regulation of the HPA axis was comparable to that of the HMS15 rats. GR mRNA was elevated in the cortex of HMS180F rats. Overall, these studies support the thesis that the long-term effects of neonatal maternal separation may largely result from alterations in the quality of maternal care rather than from direct effects of the separation per se on the pups.

Negative affect in offspring of depressed mothers is predicted by infant cortisol levels at 6 months and maternal depression during pregnancy, but not postpartum.

This study tests the hypothesis that maternal depression during pregnancy predicts temperament in offspring aged 6 m to 5 y. Previous studies have shown that maternal depression is related to negative affect and that certain temperament factors, such as negative affect and behavioral inhibition, in children predict affective disorders. Here, maternal depression is divided into depression during pregnancy vs. depression postpartum. Maternal depression was determined by the Beck Depression Inventory (BDI) throughout pregnancy and postpartum (prospectively) and by a diagnostic interview (SCID) at 6 months postpartum. The data show that maternal depression during pregnancy, but not postpartum, predicted the ratings of negative affect in the offspring. Importantly, symptoms of depression in the mother (BDI) were used as a control variable in the analyses in order to control for potential bias related to the mother's mood. In addition, cortisol levels in response to a mild stressor at 6 months of age predicted negative affect in infants and toddlers. We conclude that the effects of maternal depression on behavioral problems and vulnerability to mental illness may be mediated by altered temperament and enhanced stress responsiveness.

Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in Long Evans rats and reversal with antidepressant treatment.

RATIONALE: This study was based on the findings of a high comorbidity among anxiety and depression as well as with alcohol abuse. OBJECTIVE: To evaluate first exposure alcohol preference in a rodent model of moderate neonatal maternal separation. METHODS: Rat pups were exposed to either normal animal facility rearing (AFR) or 15 min (HMS15) or 180 min (HMS180) of maternal separation from postnatal days 2-14. The adult (>60 days) male Long Evans progeny was tested for pituitary-adrenal axis responsiveness to airpuff startle, anxiety-like behavior in the elevated plus maze, and alcohol preference using a two-bottle, free-choice test. RESULTS: In response to home cage airpuff startle, HMS180 rats displayed an elevation in the integrated adrenocorticotropic hormone and corticosterone responses. In addition, HMS180 rats spent less time in the open arms and more time in the closed arms in the elevated plus maze. HMS180 rats drank significantly less of a water-sucrose solution and significantly more of an ethanol-sucrose solution than AFR or HMS15 rats. No rearing group differences were observed in total fluid intake. The integrated corticosterone response to airpuff startle was highly correlated with ethanol consumption and there was a negative correlation between percentage of time spent in the open arms of the elevated plus maze and ethanol consumption. Treatment with the selective serotonin reuptake inhibitor paroxetine for 21 days eliminated differences in the elevated plus maze and HPA axis responsiveness, and significantly reduced the amount of ethanol consumed by the HMS180 rats, without affecting these parameters in the HMS15 rats. CONCLUSIONS: These observations suggest that this maternal separation paradigm is a good model to study the effects of early adverse experience on the development of alcohol preference and anxiety.