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      Naloxone Treatment Prevents Prenatal Stress Effects on Peritoneal Macrophage Activity in Mice Offspring

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          The present study analyzed the effects of maternal stress (PS) and/or naloxone treatment on the activity of peritoneal macrophage in male and female Swiss mice offspring. Pregnant female rats received a daily footshock (0.2 mA) and/or a naloxone injection from gestational day 15 to 19. Experiments were performed on postnatal day 30 on male and female pups. The following results were obtained in male offspring: (1) PS decreased both the index and the percentage of phagocytosis, this decrement being reversed by naloxone treatment, and (2) naloxone alone decreased the percentage of phagocytosis. The following results were obtained in female offspring: (1) PS decreased spontaneous and phorbol myristate acetate-induced macrophage oxidative burst, this decrement being reversed by naloxone pretreatment, and (2) PS decreased both the index and percentage of the phagocytosis, this effect was prevented by naloxone treatment. These data are discussed focussing on a putative neuroimmune interaction involving opioidergic systems during the ontogeny of the central nervous and immune systems.

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          Most cited references 43

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          Alterations induced by gestational stress in brain morphology and behaviour of the offspring.

           M. Weinstock (2001)
          Retrospective studies in humans suggest that chronic maternal stress during pregnancy, associated with raised plasma levels of CRH, ACTH and cortisol may increase the likelihood of preterm birth, developmental delays and behavioural abnormalities in the children. In adulthood, it may contribute to the significant association between the incidence of schizophrenia, increased left or mixed handedness, reduction in cerebral asymmetry and anomalies in brain morphology. Our studies and others have shown that prenatal stress in rats can mimic these developmental and behavioural alterations. These rats show a reduced propensity for social interaction, increased anxiety in intimidating or novel situations and a reduction in cerebral asymmetry and dopamine turnover, consistent with those in schizophrenic humans. Prenatally-stressed (PS) rats also show behaviour consistent with depression, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions. These behavioural abnormalities are associated with impaired regulation of the hypothalamic-pituitary-adrenal axis response to stress and increased CRH activity. PS males may show demasculinisation and feminisation of their sexual behaviour. The developmental and behavioural abnormalities in PS offspring could occur through sensitisation of the foetal brain by maternal stress hormones to the action of glucocorticoid and CRH and to neurotransmitters affected by them. This may have long-lasting consequences and could explain the precipitation of depressive symptoms or schizophrenia by psychosocial stress in later life. The character of the behavioural abnormalities probably depends on the timing of the maternal stress in relation to development of the particular neuronal systems.
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            Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat.

            A study was made of the effects of prenatal stress on the reactivity of the hypothalamic-pituitary adrenal (HPA) axis in male and female offspring. Rat dams were subjected to noise and light stress on an unpredictable basis throughout pregnancy. At 28 days of age mRNA for POMC, proenkephalin and prodynorphin were measured in the hypothalamus of the offspring. A marked reduction was found in POMC mRNA in PS females (PSF) but not in males (PSM), but the other mRNA's did not differ from controls (C). At 60 days of age, PSF has 3 times higher resting levels of serum corticosterone (COR) and significantly lower dexamethasone (DEX)3H hippocampal binding sites than CF. Overnight adrenalectomy abolished the difference in DEX binding. After 10 min exposure to open field PS males and females voided more fecal pellets and made fewer center entries than C offspring, testifying to increased emotionality. Open field stress caused a 3-5-fold rise in circulating COR in all groups within 15 min, which returned to baseline by 90 min in all rats except PSF. These data show that prenatal stress can cause permanent alterations in the behavior of both sexes in stressful situations but appears to cause a selective effect on the HPA axis in the female rat.
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              The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions


                Author and article information

                S. Karger AG
                October 2005
                02 November 2005
                : 81
                : 5
                : 322-328
                Pharmacology and Toxicology Laboratory, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
                88759 Neuroendocrinology 2005;81:322–328
                © 2005 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 1, References: 50, Pages: 7
                Original Paper


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