Long-Lasting Analgesia With Transdermal Fentanyl: A New Approach in Rat Neonatal Research.

With advances in neonatal care, management of prolonged pain in newborns is a daily concern. In addition to ethical considerations, pain in early life would have long-term effects and consequences. However, its treatment remains inadequate.

Could maternal perinatal atypical antipsychotic treatments program later metabolic diseases in the offspring?

An association is established between schizophrenia and the development of metabolic alterations including cardiovascular diseases, type 2 diabetes and obesity. Perinatal insults, such as undernutrition, have been shown to increase the propensity to develop these pathologies, reinforcing the idea that schizophrenia may have a neurodevelopmental origin. Moreover, the use of second generation antipsychotics (SGAs) also known as "atypical" neuroleptics has also been demonstrated to exacerbate metabolic anomalies in patients with schizophrenia.

Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups.

A growing body of evidence suggests that maternal undernutrition sensitizes the offspring to the development of energy balance metabolic disorders such as type 2 diabetes, dyslipidemia, and obesity. The present study aimed at examining the impact of maternal undernutrition on leptin plasma levels in newborn male rats and on the arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that are major leptin targets. Using a model of perinatal maternal 50% food-restricted diet (FR50) in the rat, we evaluated leptin plasma levels and hypothalamic POMC and NPY gene expression from postnatal day (PND) 4 to PND30 in both control and FR50 offspring.

HPA axis programming by maternal undernutrition in the male rat offspring.

Epidemiological and experimental studies have demonstrated that perinatal alterations such as maternal undernutrition are frequently associated with the onset of several chronic adult diseases. Although the physiological mechanisms involved in this "fetal programming" remain largely unknown, it has been shown that early exposure to undernutrition programs hypothalamic-pituitary-adrenal (HPA) axis throughout lifespan. However, the wide spectrum of experimental paradigms used (species, sex, age of the animals, and duration and severity of undernutrition exposure) has given rise to variable results that are difficult to interpret.

Perinatal maternal undernutrition programs the offspring hypothalamo-pituitary-adrenal (HPA) axis.

There is now compelling evidence, coming both from animal and human studies that an early exposure to undernutrition is frequently associated with low birth weight and programs HPA axis alterations throughout the lifespan. Although animal models have reported conflicting findings arising from differences in experimental paradigms and species, they have clearly demonstrated that such programming not only affects the brain but also the pituitary corticotrophs and the adrenal cortex. In fetuses, maternal undernutrition reduces HPA axis function and implicates a reduction of placental 11beta-HSD2 activity and a greater transplacental transfer of glucocorticoids (GRs).

Prenatal morphine exposure affects sympathoadrenal axis activity and serotonin metabolism in adult male rats both under basal conditions and after an ether inhalation stress.

We have previously shown that prenatal morphine exposure inhibited the hypothalamo-pituitary-adrenal (HPA) axis and altered the hypothalamic metabolism of serotonin during the early postnatal period in the rat and induced a chronic sympathoadrenal hyperactivity under resting conditions in adult male rats. In this study, we examined the effects of prenatal morphine exposure on the responsiveness to an acute ether inhalation stress of the sympathoadrenal and HPA axis and the hippocampal and hypothalamic concentrations of serotonin (5HT) and 5-hydroxylindoleacetic acid (5HIAA) in 3-month-old male rats. The plasma levels of adrenocorticopic hormone (ACTH) and corticosterone (B) did not differ between the two groups both under resting conditions and after ether exposure.

Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress.

Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR) antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo-pituitary-adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase.

Effects of perinatal maternal food restriction on pituitary-gonadal axis and plasma leptin level in rat pup at birth and weaning and on timing of puberty.

The effects of maternal 50% food restriction (FR) during the last week of gestation and/or lactation on pituitary-gonadal axis (at birth and weaning), on circulating levels of leptin (at weaning), and on the onset of puberty have been determined in rats at birth and at weaning. Maternal FR during pregnancy has no effect at term on the litter size, on the basal level of testosterone in male pups, and on the drastic surge of circulating testosterone that occurs 2 h after birth. At weaning, similar retardation of body growth is observed in male and female pups from mothers exposed to FR.